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Anti-inflammatory treatment of uveitis with biologicals: new treatment options that reflect pathogenetic knowledge of the disease

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Abstract

Background

Endogenous uveitis is a sight-threatening disease. In addition to corticosteroids, immunosuppressive agents are commonly used to treat patients with severe course. Immunosuppressive drugs act nonspecifically, rather than providing a specific interaction with the critical pathogenetic pathways of uveitis. Better knowledge of the basic mechanisms underlying uveitis and of the molecules that are important for regulating inflammation has helped to create new and more specific treatment approaches. Biological therapy for inflammatory diseases employs substances that interfere with specific molecules or pathways induced in the body during the inflammatory process.

Methods

This review gives an overview on molecules that play a critical role in the pathogenetic process of uveitis, as has been observed in patients or the respective animal models, and summarizes the current experience with biologicals for the treatment of uveitis refractive to conventional immunosuppressives.

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References

  1. Rothova A, Berendschot TT, Probst K, van Kooij B, Baarsma GS (2004) Birdshot chorioretinopathy: long-term manifestations and visual prognosis. Ophthalmology 111:954–959

    Article  PubMed  Google Scholar 

  2. Durrani OM, Tehrani NN, Marr JE, Moradi P, Stavrou P, Murray PI (2004) Degree, duration, and causes of visual loss in uveitis. Br J Ophthalmol 88:1159–1162

    Article  PubMed  CAS  Google Scholar 

  3. Vidovic-Valentincic N, Kraut A, Hawlina M, Stunf S, Rothova A (2009) Intermediate uveitis: long-term course and visual outcome. Br J Ophthalmol 93:477–480

    Article  PubMed  CAS  Google Scholar 

  4. Tugal Tutkun I, Onal S, Altan Yaycioglu R, Huseyin Altunbas H, Urgancioglu M (2004) Uveitis in Behcet disease: an analysis of 880 patients. Am J Ophthalmol 138:373–380

    Article  PubMed  Google Scholar 

  5. Forrester JV, Worgul BV, Merriam GR Jr (1980) Endotoxin-induced uveitis in the rat. Albrecht Von Graefes Arch Klin Exp Ophthalmol 213:221–233

    Article  PubMed  CAS  Google Scholar 

  6. Bhattacherjee P, Williams RN, Eakins KE (1983) An evaluation of ocular inflammation following the injection of bacterial endotoxin into the rat foot pad. Invest Ophthalmol Vis Sci 24:196–202

    PubMed  CAS  Google Scholar 

  7. Rosenbaum JT, McDevitt HO, Guss RB, Egbert PR (1980) Endotoxin-induced uveitis in rats as a model for human disease. Nature 286:611–613

    Article  PubMed  CAS  Google Scholar 

  8. Bhattacherjee P (1980) Prostaglandins and inflammatory reactions in the eye. Methods Find Exp Clin Pharmacol 2:17–31

    PubMed  CAS  Google Scholar 

  9. de Vos AF, van Haren MA, Verhagen C, Hoekzema R, Kijlstra A (1994) Kinetics of intraocular tumor necrosis factor and interleukin-6 in endotoxin-induced uveitis in the rat. Invest Ophthalmol Vis Sci 35:1100–1106

    PubMed  Google Scholar 

  10. Okumura A, Mochizuki M, Nishi M, Herbort CP (1990) Endotoxin-induced uveitis (EIU) in the rat: a study of inflammatory and immunological mechanisms. Int Ophthalmol 14:31–36

    Article  PubMed  CAS  Google Scholar 

  11. Hoekzema R, Murray PI, van Haren MA, Helle M, Kijlstra A (1991) Analysis of interleukin-6 in endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 32:88–95

    PubMed  CAS  Google Scholar 

  12. Ohta K, Yamagami S, Taylor AW, Streilein JW (2000) IL-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 41:2591–2599

    PubMed  CAS  Google Scholar 

  13. Forrester JV, Liversidge J, Dua HS, Towler H, McMenamin PG (1990) Comparison of clinical and experimental uveitis. Curr Eye Res 9(Suppl):75–84

    Article  PubMed  Google Scholar 

  14. Mochizuki M, Kuwabara T, McAllister C, Nussenblatt RB, Gery I (1985) Adoptive transfer of experimental autoimmune uveoretinitis in rats. Immunopathogenic mechanisms and histologic features. Invest Ophthalmol Vis Sci 26:1–9

    PubMed  CAS  Google Scholar 

  15. Xu H, Wawrousek EF, Redmond TM, Nickerson JM, Wiggert B, Chan CC, Caspi RR (2000) Transgenic expression of an immunologically privileged retinal antigen extraocularly enhances self tolerance and abrogates susceptibility to autoimmune uveitis. Eur J Immunol 30:272–278

    Article  PubMed  CAS  Google Scholar 

  16. Deeg CA, Raith AJ, Amann B, Crabb JW, Thurau SR, Hauck SM, Ueffing M, Wildner G (2007) Stangassinger M (2007) CRALB is a highly prevalent autoantigen for human autoimmune uveitis. Clin Dev Immunuol 2007:39245

    Google Scholar 

  17. Caspi RR, Roberge FG, Chan CC, Wiggert B, Chader GJ, Rozenszajn LA, Lando Z, Nussenblatt RB (1988) A new model of autoimmune disease. Experimental autoimmune uveoretinitis induced in mice with two different retinal antigens. J Immunol 140:1490–1495

    PubMed  CAS  Google Scholar 

  18. Chan CC, Caspi RR, Ni M, Leake WC, Wiggert B, Chader GJ, Nussenblatt RB (1990) Pathology of experimental autoimmune uveoretinitis in mice. J Autoimmun 3:247–255

    Article  PubMed  CAS  Google Scholar 

  19. Abbas AK, Lohr J, Knoechel B (2007) Balancing autoaggressive and protective T cell responses. J Autoimmun 28:59–61

    Article  PubMed  CAS  Google Scholar 

  20. Jiang HR, Lumsden L, Forrester JV (1999) Macrophages and dendritic cells in IRBP-induced experimental autoimmune uveoretinitis in B10RIII mice. Invest Ophthalmol Vis Sci 40:3177–3185

    PubMed  CAS  Google Scholar 

  21. Caspi RR, Roberge FG, McAllister CG, el Saied M, Kuwabara T, Gery I, Hanna E, Nussenblatt RB (1986) T cell lines mediating experimental autoimmune uveoretinitis (EAU) in the rat. J Immunol 136:928–933

    PubMed  CAS  Google Scholar 

  22. Atalla L, Linker Israeli M, Steinman L, Rao NA (1990) Inhibition of autoimmune uveitis by anti-CD4 antibody. Invest Ophthalmol Vis Sci 31:1264–1270

    PubMed  CAS  Google Scholar 

  23. Caspi RR, Chan CC, Fujino Y, Najafian F, Grover S, Hansen CT, Wilder RL (1993) Recruitment of antigen-nonspecific cells plays a pivotal role in the pathogenesis of a T cell-mediated organ-specific autoimmune disease, experimental autoimmune uveoretinitis. J Neuroimmunol 47:177–188

    Article  PubMed  CAS  Google Scholar 

  24. Luger D, Silver PB, Tang J, Cua D, Chen Z, Iwakura Y, Bowman EP, Sgambellone NM, Chan CC, Caspi RR (2008) Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. J Exp Med 205:799–810

    Article  PubMed  CAS  Google Scholar 

  25. Wildner G, Diedrichs-Mohring M, Thurau SR (2002) Induction of arthritis and uveitis in Lewis rats by antigenic mimicry of peptides from HLA-B27 and cytokeratin. Eur J Immunol 32:299–306

    Article  PubMed  CAS  Google Scholar 

  26. Wildner G, Diedrichs Mohring M (2003) Autoimmune uveitis induced by molecular mimicry of peptides from rotavirus, bovine casein and retinal S-antigen. Eur J Immunol 33:2577–2587

    Article  PubMed  CAS  Google Scholar 

  27. O'Shea JJ, Ma A, Lipsky P (2002) Cytokines and autoimmunity. Nat Rev Immunol 2:37–45

    Article  PubMed  CAS  Google Scholar 

  28. Eigler A, Sinha B, Hartmann G, Endres S (1997) Taming TNF: strategies to restrain this proinflammatory cytokine. Immunol Today 18:487–492

    Article  PubMed  CAS  Google Scholar 

  29. Hehlgans T, Mannel DN (2002) The TNF-TNF receptor system. Biol Chem 383:1581–1585

    Article  PubMed  CAS  Google Scholar 

  30. Palladino MA, Bahjat FR, Theodorakis EA, Moldawer LL (2003) Anti-TNF-alpha therapies: the next generation. Nat Rev Drug Discov 2:736–746

    Article  PubMed  CAS  Google Scholar 

  31. Eissner G, Kolch W, Scheurich P (2004) Ligands working as receptors: reverse signaling by members of the TNF superfamily enhance the plasticity of the immune system. Cytokine Growth Factor Rev 15:353–366

    Article  PubMed  CAS  Google Scholar 

  32. Akassoglou K, Probert L, Kontogeorgos G, Kollias G (1997) Astrocyte-specific but not neuron-specific transmembrane TNF triggers inflammation and degeneration in the central nervous system of transgenic mice. J Immunol 158:438–445

    PubMed  CAS  Google Scholar 

  33. Kuno R, Wang J, Kawanokuchi J, Takeuchi H, Mizuno T, Suzumura A (2005) Autocrine activation of microglia by tumor necrosis factor-alpha. J Neuroimmunol 162:89–96

    Article  PubMed  CAS  Google Scholar 

  34. Tamatani M, Che YH, Matsuzaki H, Ogawa S, Okado H, Miyake S, Mizuno T, Tohyama M (1999) Tumor necrosis factor induces Bcl-2 and Bcl-x expression through NFkappaB activation in primary hippocampal neurons. J Biol Chem 274:8531–8538

    Article  PubMed  CAS  Google Scholar 

  35. Singer OC, Otto B, Steinmetz H, Ziemann U (2004) Acute neuropathy with multiple conduction blocks after TNFalpha monoclonal antibody therapy. Neurology 63:1754

    PubMed  Google Scholar 

  36. The Lenercept Multiple Sclerosis Study Group, The University of British Columbia MS/MRI Analysis Group (1999) TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. Neurology 53:457–465

    Google Scholar 

  37. Lim WS, Powell RJ, Johnston ID (2002) Tuberculosis and treatment with infliximab. N Engl J Med 346:623–626

    Article  PubMed  Google Scholar 

  38. Mikuls TR, Moreland LW (2003) Benefit-risk assessment of infliximab in the treatment of rheumatoid arthritis. Drug Saf 26:23–32

    Article  PubMed  CAS  Google Scholar 

  39. Foroozan R, Buono LM, Sergott RC, Savino PJ (2002) Retrobulbar optic neuritis associated with infliximab. Arch Ophthalmol 120:985–987

    PubMed  Google Scholar 

  40. El Shabrawi Y, Hermann J (2002) Anti-tumor necrosis factor-alpha therapy with infliximab as an alternative to corticosteroids in the treatment of human leukocyte antigen B27-associated acute anterior uveitis. Ophthalmology 109:2342–2346

    Article  PubMed  Google Scholar 

  41. Fries W, Giofre MR, Catanoso M, Lo Gullo R (2002) Treatment of acute uveitis associated with Crohn's disease and sacroileitis with infliximab. Am J Gastroenterol 97:499–500

    Article  PubMed  Google Scholar 

  42. Braun J, Baraliakos X, Listing J, Sieper J (2005) Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept. Arthritis Rheum 52:2447–2451

    Article  PubMed  CAS  Google Scholar 

  43. Guignard S, Gossec L, Salliot C, Ruyssen-Witrand A, Luc M, Duclos M, Dougados M (2006) Efficacy of tumour necrosis factor blockers in reducing uveitis flares in patients with spondylarthropathy: a retrospective study. Ann Rheum Dis 65:1631–1634

    Article  PubMed  CAS  Google Scholar 

  44. Joseph A, Raj D, Dua HS, Powell PT, Lanyon PC, Powell RJ (2003) Infliximab in the treatment of refractory posterior uveitis. Ophthalmology 110:1449–1453

    Article  PubMed  Google Scholar 

  45. Sfikakis PP (2002) Behcet's disease: a new target for anti-tumour necrosis factor treatment. Ann Rheum Dis 61(Suppl 2):ii51–ii53

    PubMed  Google Scholar 

  46. Tabbara KF, Al-Hemidan AI (2008) Infliximab effects compared to conventional therapy in the management of retinal vasculitis in Behcet disease. Am J Ophthalmol 146:845–850

    Article  PubMed  CAS  Google Scholar 

  47. Al-Rayes H, Al-Swailem R, Al-Balawi M, Al-Dohayan N, Al-Zaidi S, Tariq M (2008) Safety and efficacy of infliximab therapy in active Behcet's uveitis: an open-label trial. Rheumatol Int 29:53–57

    Article  PubMed  CAS  Google Scholar 

  48. Tognon S, Graziani G, Marcolongo R (2007) Anti-TNF-alpha therapy in seven patients with Behcet's uveitis: advantages and controversial aspects. Ann NY Acad Sci 1110:474–484

    Article  PubMed  CAS  Google Scholar 

  49. Accorinti M, Pirraglia MP, Paroli MP, Priori R, Conti F, Pivetti-Pezzi P (2007) Infliximab treatment for ocular and extraocular manifestations of Behcet's disease. Jpn J Ophthalmol 51:191–196

    Article  PubMed  CAS  Google Scholar 

  50. Niccoli L, Nannini C, Benucci M, Chindamo D, Cassara E, Salvarani C, Cimino L, Gini G, Lenzetti I, Cantini F (2007) Long-term efficacy of infliximab in refractory posterior uveitis of Behcet's disease: a 24-month follow-up study. Rheumatology (Oxford) 46:1161–1164

    Article  CAS  Google Scholar 

  51. Gallagher M, Quinones K, Cervantes-Castaneda RA, Yilmaz T, Foster CS (2007) Biological response modifier therapy for refractory childhood uveitis. Br J Ophthalmol 91:1341–1344

    Article  PubMed  Google Scholar 

  52. Sharma SM, Ramanan AV, Riley P, Dick AD (2007) Use of infliximab in juvenile onset rheumatological disease-associated refractory uveitis: efficacy in joint and ocular disease. Ann Rheum Dis 66:840–841

    Article  PubMed  CAS  Google Scholar 

  53. Simonini G, Zannin ME, Caputo R, Falcini F, de Martino M, Zulian F, Cimaz R (2008) Loss of efficacy during long-term infliximab therapy for sight-threatening childhood uveitis. Rheumatology (Oxford) 47:1510–1514

    Article  CAS  Google Scholar 

  54. Tynjala P, Lindahl P, Honkanen V, Lahdenne P, Kotaniemi K (2007) Infliximab and etanercept in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis. Ann Rheum Dis 66:548–550

    Article  PubMed  CAS  Google Scholar 

  55. Elewaut D, Van den Bosch F, Verbruggen G, de Keyser F, Cruyssen BV, Mielants H (2009) Clinical observations programme in SpA: disease parameters, treatment options and practical management issues. Rheumatol Int 29:239–250

    Article  PubMed  Google Scholar 

  56. Rudwaleit M, Rodevand E, Holck P, Vanhoof J, Kron M, Kary S, Kupper H (2009) Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study. Ann Rheum Dis 68:696–701, Epub 2008 Jul 28

    Article  PubMed  CAS  Google Scholar 

  57. Tynjala P, Kotaniemi K, Lindahl P, Latva K, Aalto K, Honkanen V, Lahdenne P (2008) Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis. Rheumatology (Oxford) 47:339–344

    Article  CAS  Google Scholar 

  58. Biester S, Deuter C, Michels H, Haefner R, Kuemmerle-Deschner J, Doycheva D, Zierhut M (2007) Adalimumab in the therapy of uveitis in childhood. Br J Ophthalmol 91:319–324

    Article  PubMed  Google Scholar 

  59. Foster CS, Tufail F, Waheed NK, Chu D, Miserocchi E, Baltatzis S, Vredeveld CM (2003) Efficacy of etanercept in preventing relapse of uveitis controlled by methotrexate. Arch Ophthalmol 121:437–440

    Article  PubMed  CAS  Google Scholar 

  60. Petropoulos IK, Vaudaux JD, Guex-Crosier Y (2008) Anti-TNF-alpha therapy in patients with chronic non-infectious uveitis: the experience of Jules Gonin Eye Hospital. Klin Monatsbl Augenheilkd 225:457–461

    Article  PubMed  CAS  Google Scholar 

  61. Galor A, Perez VL, Hammel JP, Lowder CY (2006) Differential effectiveness of etanercept and infliximab in the treatment of ocular inflammation. Ophthalmology 113:2317–2323

    Article  PubMed  Google Scholar 

  62. Smith JA, Thompson DJ, Whitcup SM, Suhler E, Clarke G, Smith S, Rbinson M, Kim J, Barron KS (2005) A randomized, placebo-controlled, double-masked clinical trial of etenercept for the treatment of uveitis associated with juvenile idiopatihic arthritis. Arthritis Rheum 53:18–23

    Article  PubMed  CAS  Google Scholar 

  63. Reiff A (2003) Long-term outcome of etanercept therapy in children with treatment-refractory uveitis. Arthritis Rheum 48:2079–2080

    Article  PubMed  Google Scholar 

  64. Cobo-Ibanez T, del Carmen OM, Munoz-Fernandez S, Madero-Prado R, Martin-Mola E (2008) Do TNF-blockers reduce or induce uveitis? Rheumatology (Oxford) 47:731–732

    Article  CAS  Google Scholar 

  65. Reddy AR, Backhouse OC (2003) Does etanercept induce uveitis? Br J Ophthalmol 87:925

    Article  PubMed  CAS  Google Scholar 

  66. Taban M, Dupps WJ, Mandell B, Perez VL, Taban M, Dupps WJ, Mandell B, Perez VL (2006) Etanercept (enbrel)-associated inflammatory eye disease: case report and review of the literature. Ocul Immunol Inflamm 14:145–150

    Article  PubMed  Google Scholar 

  67. Lim LL, Fraunfelder FW, Rosenbaum JT (2007) Do tumor necrosis factor inhibitors cause uveitis? A registry-based study. Arthritis Rheum 56:3248–3252

    Article  PubMed  CAS  Google Scholar 

  68. Paul-Pletzer K (2006) Tocilizumab: blockade of interleukin-6 signaling pathway as a therapeutic strategy for inflammatory disorders. Drugs Today (Barc) 42:559–576

    Article  CAS  Google Scholar 

  69. Mima T, Nishimoto N (2009) Clinical value of blocking IL-6 receptor. Curr Opin Rheumatol 21:224–230

    Article  PubMed  CAS  Google Scholar 

  70. Mangan PR, Harrington LE, O'Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, Wahl SM, Schoeb TR, Weaver CT (2006) Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441:231–234

    Article  PubMed  CAS  Google Scholar 

  71. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–238

    Article  PubMed  CAS  Google Scholar 

  72. Nakahara H, Song J, Sugimoto M, Hagihara K, Kishimoto T, Yoshizaki K, Nishimoto N (2003) Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis. Arthritis Rheum 48:1521–1529

    Article  PubMed  CAS  Google Scholar 

  73. Ishihara K, Hirano T (2002) IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev 13:357–368

    Article  PubMed  CAS  Google Scholar 

  74. Nishimoto N, Kishimoto T (2006) Interleukin 6: from bench to bedside. Nat Clin Pract Rheumatol 2:619–626

    Article  PubMed  CAS  Google Scholar 

  75. Kitani A, Hara M, Hirose T, Harigai M, Suzuki K, Kawakami M, Kawaguchi Y, Hidaka T, Kawagoe M, Nakamura H (1992) Autostimulatory effects of IL-6 on excessive B cell differentiation in patients with systemic lupus erythematosus: analysis of IL-6 production and IL-6R expression. Clin Exp Immunol 88:75–83

    Article  PubMed  CAS  Google Scholar 

  76. Nagafuchi H, Suzuki N, Mizushima Y, Sakane T (1993) Constitutive expression of IL-6 receptors and their role in the excessive B cell function in patients with systemic lupus erythematosus. J Immunol 151:6525–6534

    PubMed  CAS  Google Scholar 

  77. Yoshimura T, Sonoda K-H, Ohguro N, Ohsugi Y, Ishibashi T, Cua DJ, Kobayashi T, Yoshida H, Yoshimura A (2009) Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis. Rheumatology 48:347–354

    Article  PubMed  CAS  Google Scholar 

  78. Perez VL, Papaliodis GN, Chu D, Anzaar F, Christen W, Foster CS (2004) Elevated levels of interleukin 6 in the vitreous fluid of patients with pars planitis and posterior uveitis: the Massachusetts eye & ear experience and review of previous studies. Ocul Immunol Inflamm 12:193–201

    Article  PubMed  CAS  Google Scholar 

  79. Iwanami K, Matsumoto I, Tanaka-Watanabe Y, Inoue A, Mihara M, Ohsugi Y, Mamura M, Goto D, Ito S, Tsutsumi A, Kishimoto T, Sumida T (2008) Crucial role of the interleukin-6/interleukin-17 cytokine axis in the induction of arthritis by glucose-6-phosphate isomerase. Arthritis Rheum 58:754–763

    Article  PubMed  CAS  Google Scholar 

  80. Serada S, Fujimoto M, Mihara M, Koike N, Ohsugi Y, Nomura S, Yoshida H, Nishikawa T, Terabe F, Ohkawara T, Takahashi T, Ripley B, Kimura A, Kishimoto T, Naka T (2008) IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 105:9041–9046

    Article  PubMed  Google Scholar 

  81. Sato K, Tsuchiya M, Saldanha J, Koishihara Y, Ohsugi Y, Kishimoto T, Bendig MM (1993) Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth. Cancer Res 53:851–856

    PubMed  CAS  Google Scholar 

  82. Ohsugi Y, Kishimoto T (2008) The recombinant humanized anti-IL-6 receptor antibody tocilizumab, an innovative drug for the treatment of rheumatoid arthritis. Expert Opin Biol Ther 8:669–681

    Article  PubMed  CAS  Google Scholar 

  83. Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J (2009) Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study. Ann Rheum Dis 68:1580–1584

    Article  PubMed  CAS  Google Scholar 

  84. Yokota S (2003) Interleukin 6 as a therapeutic target in systemic-onset juvenile idiopathic arthritis. Curr Opin Rheumatol 15:581–586

    Article  PubMed  CAS  Google Scholar 

  85. Dong C, Flavell RA (2000) Cell fate decision: T-helper 1 and 2 subsets in immune responses. Arthritis Res 2:179–188

    Article  PubMed  CAS  Google Scholar 

  86. Glimcher LH, Murphy KM (2000) Lineage commitment in the immune system: the T helper lymphocyte grows up. Genes Dev 14:1693–1711

    PubMed  CAS  Google Scholar 

  87. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132

    Article  PubMed  CAS  Google Scholar 

  88. Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, Levy DE, Leonard WJ, Littman DR (2007) IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8:967–974

    Article  PubMed  CAS  Google Scholar 

  89. Starnes T, Robertson MJ, Sledge G, Kelich S, Nakshatri H, Broxmeyer HE, Hromas R (2001) Cutting edge: IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production. J Immunol 167:4137–4140

    PubMed  CAS  Google Scholar 

  90. Iwakura Y, Nakae S, Saijo S, Ishigame H (2008) The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunol Rev 226:57–79

    Article  PubMed  CAS  Google Scholar 

  91. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201:233–240

    Article  PubMed  CAS  Google Scholar 

  92. Iwakura Y, Ishigame H (2006) The IL-23/IL-17 axis in inflammation. J Clin Invest 116:1218–1222

    Article  PubMed  CAS  Google Scholar 

  93. Guo B, Chang EY, Cheng G (2008) The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice. J Clin Invest 118:1680–1690

    Article  PubMed  CAS  Google Scholar 

  94. Stumhofer JS, Laurence A, Wilson EH, Huang E, Tato CM, Johnson LM, Villarino AV, Huang Q, Yoshimura A, Sehy D, Saris CJ, O'Shea JJ, Hennighausen L, Ernst M, Hunter CA (2006) Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol 7:937–945

    Article  PubMed  CAS  Google Scholar 

  95. Fossiez F, Banchereau J, Murray R, Van Kooten C, Garrone P, Lebecque S (1998) Interleukin-17. Int Rev Immunol 16:541–551

    Article  PubMed  CAS  Google Scholar 

  96. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421:744–748

    Article  PubMed  CAS  Google Scholar 

  97. Lock C, Hermans G, Pedotti R, Brendolan A, Schadt E, Garren H, Langer-Gould A, Strober S, Cannella B, Allard J, Klonowski P, Austin A, Lad N, Kaminski N, Galli SJ, Oksenberg JR, Raine CS, Heller R, Steinman L (2002) Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 8:500–508

    Article  PubMed  CAS  Google Scholar 

  98. Ishizu T, Osoegawa M, Mei FJ, Kikuchi H, Tanaka M, Takakura Y, Minohara M, Murai H, Mihara F, Taniwaki T, Kira J (2005) Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis. Brain 128:988–1002

    Article  PubMed  Google Scholar 

  99. Feldmann M, Brennan FM, Maini RN (1996) Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 14:397–440

    Article  PubMed  CAS  Google Scholar 

  100. Feldmann M, Maini SR (2008) Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeutics. Immunol Rev 223:7–19

    Article  PubMed  CAS  Google Scholar 

  101. Tesmer LA, Lundy SK, Sarkar S, Fox DA (2008) Th17 cells in human disease. Immunol Rev 223:87–113

    Article  PubMed  CAS  Google Scholar 

  102. Hamzaoui K, Hamzaoui A, Guemira F, Bessioud M, Hamza M, Ayed K (2002) Cytokine profile in Behcet's disease patients. Relationship with disease activity. Scand J Rheumatol 31:205–210

    Article  PubMed  Google Scholar 

  103. Chi W, Zhu X, Yang P, Liu X, Lin X, Zhou H, Huang X, Kijlstra A (2008) Upregulated IL-23 and IL-17 in Behcet patients with active uveitis. Invest Ophthalmol Vis Sci 49:3058–3064

    Article  PubMed  Google Scholar 

  104. Amadi-Obi A, Yu CR, Liu X, Mahdi RM, Clarke GL, Nussenblatt RB, Gery I, Lee YS, Egwuagu CE (2007) TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med 13:711–718

    Article  PubMed  CAS  Google Scholar 

  105. Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550

    Article  PubMed  CAS  Google Scholar 

  106. Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J (2005) Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med 201:1479–1486

    Article  PubMed  CAS  Google Scholar 

  107. Fitzgerald AA, Leclercq SA, Yan A, Homik JE, Dinarello CA (2005) Rapid responses to anakinra in patients with refractory adult-onset Still's disease. Arthritis Rheum 52:1794–1803

    Article  PubMed  CAS  Google Scholar 

  108. Fleischmann RM, Schechtman J, Bennett R, Handel ML, Burmester GR, Tesser J, Modafferi D, Poulakos J, Sun G (2003) Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo-controlled trial. Arthritis Rheum 48:927–934

    Article  PubMed  CAS  Google Scholar 

  109. Botsios C, Sfriso P, Furlan A, Punzi L, Dinarello CA (2008) Resistant Behcet disease responsive to anakinra. Ann Intern Med 149:284–286

    PubMed  Google Scholar 

  110. El Shabrawi YG, Christen WG, Foster SC (2000) Correlation of metalloproteinase-2 and -9 with proinflammatory cytokines interleukin-1b, interleukin-12 and the interleukin-1 receptor antagonist in patients with chronic uveitis. Curr Eye Res 20:211–214

    PubMed  CAS  Google Scholar 

  111. Foxman EF, Zhang M, Hurst SD, Muchamuel T, Shen D, Wawrousek EF, Chan CC, Gery I (2002) Inflammatory mediators in uveitis: differential induction of cytokines and chemokines in Th1- versus Th2-mediated ocular inflammation. J Immunol 168:2483–2492

    PubMed  CAS  Google Scholar 

  112. Rosenbaum JT, Boney RS (1992) Activity of an interleukin 1 receptor antagonist in rabbit models of uveitis. Arch Ophthalmol 110:547–549

    PubMed  CAS  Google Scholar 

  113. Lim WK, Fujimoto C, Ursea R, Mahesh SP, Silver P, Chan CC, Gery I, Nussenblatt RB (2005) Suppression of immune-mediated ocular inflammation in mice by interleukin 1 receptor antagonist administration. Arch Ophthalmol 123:957–963

    Article  PubMed  CAS  Google Scholar 

  114. Benezra D, Maftzir G, Barak V (1997) Blood serum interleukin-1 receptor antagonist in pars planitis and ocular Behcet disease. Am J Ophthalmol 123:593–598

    PubMed  CAS  Google Scholar 

  115. Teoh SC, Sharma S, Hogan A, Lee R, Ramanan AV, Dick AD (2007) Tailoring biological treatment: anakinra treatment of posterior uveitis associated with the CINCA syndrome. Br J Ophthalmol 91:263–264

    Article  PubMed  CAS  Google Scholar 

  116. Li Z, Lim WK, Mahesh SP, Liu B, Nussenblatt RB (2005) Cutting edge: in vivo blockade of human IL-2 receptor induces expansion of CD56(bright) regulatory NK cells in patients with active uveitis. J Immunology 174:5187–5191

    CAS  Google Scholar 

  117. Laurence A, Tato CM, Davidson TS, Kanno Y, Chen Z, Yao Z, Blank RB, Meylan F, Siegel R, Hennighausen L, Shevach EM, O'Shea JJ (2007) Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26:371–381

    Article  PubMed  CAS  Google Scholar 

  118. Tkaczuk J, Yu CL, Baksh S, Milford EL, Carpenter CB, Burakoff SJ, McKay DB (2002) Effect of anti-IL-2R alpha antibody on IL-2-induced Jak/STAT signaling. Am J Transplant 2:31–40

    Article  PubMed  CAS  Google Scholar 

  119. Oh U, Blevins G, Griffith C, Richert N, Maric D, Lee CR, McFarland H, Jacobson S (2009) Regulatory T cells are reduced during anti-CD25 antibody treatment of multiple sclerosis. Arch Neurol 66:471–479

    Article  PubMed  Google Scholar 

  120. Moore AC, Gallimore A, Draper SJ, Watkins KR, Gilbert SC, Hill AV (2005) Anti-CD25 antibody enhancement of vaccine-induced immunogenicity: increased durable cellular immunity with reduced immunodominance. J Immunol 175:7264–7273

    PubMed  CAS  Google Scholar 

  121. Rech AJ, Vonderheide RH (2009) Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells. Ann NY Acad Sci 1174:99–106

    Article  PubMed  CAS  Google Scholar 

  122. Guex Crosier Y, Raber J, Chan CC, Kriete MS, Benichou J, Pilson RS, Kerwin JA, Waldmann TA, Hakimi J, Roberge FG (1997) Humanized antibodies against the alpha-chain of the IL-2 receptor and against the beta-chain shared by the IL-2 and IL-15 receptors in a monkey uveitis model of autoimmune diseases. J Immunol 158:452–458

    PubMed  CAS  Google Scholar 

  123. Nussenblatt RB, Fortin E, Schiffman R, Rizzo L, Smith J, Van Veldhuisen P, Sran P, Yaffe A, Goldman CK, Waldmann TA, Whitcup SM (1999) Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: a phase I/II clinical trial. Proc Natl Acad Sci USA 96:7462–7466

    Article  PubMed  CAS  Google Scholar 

  124. Sen HN, Levy-Clarke G, Faia LJ, Li Z, Yeh S, Barron KS, Ryan JG, Hammel K, Nussenblatt RB (2009) High-dose daclizumab for the treatment of juvenile idiopathic arthritis-associated active anterior uveitis. Am J Ophthalmol 148:696–703

    Article  PubMed  CAS  Google Scholar 

  125. Bhat P, Castaneda-Cervantes RA, Doctor PP, Foster CS (2009) Intravenous daclizumab for recalcitrant ocular inflammatory disease. Graefes Arch Clin Exp Ophthalmol 247:687–692

    Article  PubMed  CAS  Google Scholar 

  126. Yeh S, Wroblewski K, Buggage R, Li Z, Kurup SK, Sen HN, Dahr S, Sran P, Reed GF, Robinson R, Ragheb JA, Waldmann TA, Nussenblatt RB (2008) High-dose humanized anti-IL-2 receptor alpha antibody (daclizumab) for the treatment of active, non-infectious uveitis. J Autoimmun 31:91–97

    Article  PubMed  CAS  Google Scholar 

  127. Sobrin L, Huang JJ, Christen W, Kafkala C, Choopong P, Foster CS (2008) Daclizumab for treatment of birdshot chorioretinopathy. Arch Ophthalmol 126:186–191

    Article  PubMed  CAS  Google Scholar 

  128. Buggage RR, Levy-Clarke G, Sen HN, Ursea R, Srivastava SK, Suhler EB, Altemare C, Velez G, Ragheb J, Chan C-C, Nussenblatt RB, Bamji AT, Sran P, Waldmann T, Thompson DJS (2007) A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Behcet's disease. Ocul Immunol Inflamm 15:63–70

    Article  PubMed  CAS  Google Scholar 

  129. Papaliodis GN, Chu D, Foster CS (2003) Treatment of ocular inflammatory disorders with daclizumab. Ophthalmology 110:786–789

    Article  PubMed  Google Scholar 

  130. Stamper CC, Zhang Y, Tobin JF, Erbe DV, Ikemizu S, Davis SJ, Stahl ML, Seehra J, Somers WS, Mosyak L (2001) Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses. Nature 410:608–611

    Article  PubMed  CAS  Google Scholar 

  131. Perkins D, Wang Z, Donovan C, He H, Mark D, Guan G, Wang Y, Walunas T, Bluestone J, Listman J, Finn PW (1996) Regulation of CTLA-4 expression during T cell activation. J Immunol 156:4154–4159

    PubMed  CAS  Google Scholar 

  132. Takahashi T, Tagami T, Yamazaki S, Uede T, Shimizu J, Sakaguchi N, Mak TW, Sakaguchi S (2000) Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 192:303–310

    Article  PubMed  CAS  Google Scholar 

  133. Reiser H, Stadecker MJ (1996) Costimulatory B7 molecules in the pathogenesis of infectious and autoimmune diseases. N Engl J Med 335:1369–1377

    Article  PubMed  CAS  Google Scholar 

  134. Linsley PS, Wallace PM, Johnson J, Gibson MG, Greene JL, Ledbetter JA, Singh C, Tepper MA (1992) Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science 257:792–795

    Article  PubMed  CAS  Google Scholar 

  135. Genovese MC, Schiff M, Luggen M, Becker JC, Aranda R, Teng J, Li T, Schmidely N, Le Bars M, Dougados M (2008) Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy. Ann Rheum Dis 67:547–554

    Article  PubMed  CAS  Google Scholar 

  136. Weber J (2007) Review: anti-CTLA-4 antibody ipilimumab: case studies of clinical response and immune-related adverse events. Oncologist 12:864–872

    Article  PubMed  CAS  Google Scholar 

  137. Angeles-Han S, Flynn T, Lehman T (2008) Abatacept for refractory juvenile idiopathic arthritis-associated uveitis—a case report. J Rheumatol 35:1897–1898

    PubMed  Google Scholar 

  138. Furuzawa-Carballeda J, Alcocer-Varela J (1999) Interleukin-8, interleukin-10, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression levels are higher in synovial tissue from patients with rheumatoid arthritis than in osteoarthritis. Scand J Immunol 50:215–222

    Article  PubMed  CAS  Google Scholar 

  139. Wellicome SM, Kapahi P, Mason JC, Lebranchu Y, Yarwood H, Haskard DO (1993) Detection of a circulating form of vascular cell adhesion molecule-1: raised levels in rheumatoid arthritis and systemic lupus erythematosus. Clin Exp Immunol 92:412–418

    Article  PubMed  CAS  Google Scholar 

  140. Kitani A, Nakashima N, Izumihara T, Inagaki M, Baoui X, Yu S, Matsuda T, Matsuyama T (1998) Soluble VCAM-1 induces chemotaxis of Jurkat and synovial fluid T cells bearing high affinity very late antigen-4. J Immunol 161:4931–4938

    PubMed  CAS  Google Scholar 

  141. Li XC, Jevnikar AM, Grant DR (1997) Expression of functional ICAM-1 and VCAM-1 adhesion molecules by an immortalized epithelial cell clone derived from the small intestine. Cell Immunol 175:58–66

    Article  PubMed  CAS  Google Scholar 

  142. Hafezi-Moghadam A, Noda K, Almulki L, Iliaki EF, Poulaki V, Thomas KL, Nakazawa T, Hisatomi T, Miller JW, Gragoudas ES (2007) VLA-4 blockade suppresses endotoxin-induced uveitis: in vivo evidence for functional integrin up-regulation. FASEB J 21:464–474

    Article  PubMed  CAS  Google Scholar 

  143. La Heij E, Kuijpers RW, Baarsma SG, Kijlstra A, van der Weiden M, Mooy CM (1998) Adhesion molecules in iris biopsy specimens from patients with uveitis. Br J Ophthalmol 82:432–437

    Article  PubMed  Google Scholar 

  144. Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354:899–910

    Article  PubMed  CAS  Google Scholar 

  145. Guagnozzi D, Caprilli R (2008) Natalizumab in the treatment of Crohn's disease. Biologics 2:275–284

    PubMed  CAS  Google Scholar 

  146. Parkos CA, Colgan SP, Diamond MS, Nusrat A, Liang TW, Springer TA, Madara JL (1996) Expression and polarization of intercellular adhesion molecule-1 on human intestinal epithelia: consequences for CD11b/CD18-mediated interactions with neutrophils. Mol Med 2:489–505

    PubMed  CAS  Google Scholar 

  147. Vainer B, Nielsen OH (2000) Changed colonic profile of P-selectin, platelet-endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), ICAM-2, and ICAM-3 in inflammatory bowel disease. Clin Exp Immunol 121:242–247

    Article  PubMed  CAS  Google Scholar 

  148. Whitcup SM, Hikita N, Shirao M, Miyasaka M, Tamatani T, Mochizuki M, Nussenblatt RB, Chan CC (1995) Monoclonal antibodies against CD54 (ICAM-1) and CD11a (LFA-1) prevent and inhibit endotoxin-induced uveitis. Exp Eye Res 60:597–601

    Article  PubMed  CAS  Google Scholar 

  149. Whitcup SM, DeBarge LR, Caspi RR, Harning R, Nussenblatt RB, Chan CC (1993) Monoclonal antibodies against ICAM-1 (CD54) and LFA-1 (CD11a/CD18) inhibit experimental autoimmune uveitis. Clin Immunol Immunopathol 67:143–150

    Article  PubMed  CAS  Google Scholar 

  150. Crooke ST (2004) Progress in antisense technology. Annu Rev Med 55:61–95

    Article  PubMed  CAS  Google Scholar 

  151. Wu H, Lima WF, Zhang H, Fan A, Sun H, Crooke ST (2004) Determination of the role of the human RNase H1 in the pharmacology of DNA-like antisense drugs. J Biol Chem 279:17181–17189

    Article  PubMed  CAS  Google Scholar 

  152. Yacyshyn B, Chey WY, Wedel MK, Yu RZ, Paul D, Chuang E (2007) A randomized, double-masked, placebo-controlled study of alicaforsen, an antisense inhibitor of intercellular adhesion molecule 1, for the treatment of subjects with active Crohn's disease. Clin Gastroenterol Hepatol 5:215–220

    Article  PubMed  CAS  Google Scholar 

  153. Leonardi CL (2003) Efalizumab: an overview. J Am Acad Dermatol 49:S98–S104

    Article  PubMed  Google Scholar 

  154. Dorner T, Burmester GR (2003) The role of B cells in rheumatoid arthritis: mechanisms and therapeutic targets. Curr Opin Rheumatol 15:246–252

    Article  PubMed  Google Scholar 

  155. Edwards JC, Cambridge G, Abrahams VM (1999) Do self-perpetuating B lymphocytes drive human autoimmune disease? Immunology 97:188–196

    Article  PubMed  CAS  Google Scholar 

  156. Shaw T, Quan J, Totoritis MC (2003) B cell therapy for rheumatoid arthritis: the rituximab (anti-CD20) experience. Ann Rheum Dis 62(Suppl 2):ii55–ii59

    PubMed  CAS  Google Scholar 

  157. Takemura S, Klimiuk PA, Braun A, Goronzy JJ, Weyand CM (2001) T cell activation in rheumatoid synovium is B cell dependent. J Immunol 167:4710–4718

    PubMed  CAS  Google Scholar 

  158. Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, Newman RA, Hanna N, Anderson DR (1994) Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83:435–445

    PubMed  CAS  Google Scholar 

  159. Taylor RP, Lindorfer MA (2008) Immunotherapeutic mechanisms of anti-CD20 monoclonal antibodies. Curr Opin Immunol 20:444–449

    Article  PubMed  CAS  Google Scholar 

  160. DiLillo DJ, Hamaguchi Y, Ueda Y, Yang K, Uchida J, Haas KM, Kelsoe G, Tedder TF (2008) Maintenance of long-lived plasma cells and serological memory despite mature and memory B cell depletion during CD20 immunotherapy in mice. J Immunol 180:361–371

    PubMed  CAS  Google Scholar 

  161. Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 350:2572–2581

    Article  PubMed  CAS  Google Scholar 

  162. Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, Keystone EC, Loveless JE, Burmester GR, Cravets MW, Hessey EW, Shaw T, Totoritis MC (2006) Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 54:2793–2806

    Article  PubMed  CAS  Google Scholar 

  163. Emery P, Fleischmann R, Filipowicz-Sosnowska A, Schechtman J, Szczepanski L, Kavanaugh A, Racewicz AJ, van Vollenhoven RF, Li NF, Agarwal S, Hessey EW, Shaw TM (2006) The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum 54:1390–1400

    Article  PubMed  CAS  Google Scholar 

  164. Ng KP, Leandro MJ, Edwards JC, Ehrenstein MR, Cambridge G, Isenberg DA (2006) Repeated B cell depletion in treatment of refractory systemic lupus erythematosus. Ann Rheum Dis 65:942–945

    Article  PubMed  CAS  Google Scholar 

  165. Jonsdottir T, Gunnarsson I, Risselada A, Henriksson EW, Klareskog L, van Vollenhoven RF (2008) Treatment of refractory SLE with rituximab plus cyclophosphamide: clinical effects, serological changes, and predictors of response. Ann Rheum Dis 67:330–334

    Article  PubMed  CAS  Google Scholar 

  166. Albert D, Dunham J, Khan S, Stansberry J, Kolasinski S, Tsai D, Pullman-Mooar S, Barnack F, Striebich C, Looney RJ, Prak ET, Kimberly R, Zhang Y, Eisenberg R (2008) Variability in the biological response to anti-CD20 B cell depletion in systemic lupus erythaematosus. Ann Rheum Dis 67:1724–1731

    Article  PubMed  CAS  Google Scholar 

  167. Lovric S, Erdbruegger U, Kumpers P, Woywodt A, Koenecke C, Wedemeyer H, Haller H, Haubitz M (2009) Rituximab as rescue therapy in anti-neutrophil cytoplasmic antibody-associated vasculitis: a single-centre experience with 15 patients. Nephrol Dial Transplant 24:179–185

    Article  PubMed  CAS  Google Scholar 

  168. Keogh KA, Ytterberg SR, Fervenza FC, Carlson KA, Schroeder DR, Specks U (2006) Rituximab for refractory Wegener's granulomatosis: report of a prospective, open-label pilot trial. Am J Respir Crit Care Med 173:180–187

    Article  PubMed  CAS  Google Scholar 

  169. Stasi R, Stipa E, Del Poeta G, Amadori S, Newland AC, Provan D (2006) Long-term observation of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis treated with rituximab. Rheumatology (Oxford) 45:1432–1436

    Article  CAS  Google Scholar 

  170. Dass S, Bowman SJ, Vital EM, Ikeda K, Pease CT, Hamburger J, Richards A, Rauz S, Emery P (2008) Reduction of fatigue in Sjogren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study. Ann Rheum Dis 67:1541–1544

    Article  PubMed  CAS  Google Scholar 

  171. Meijer JM, Pijpe J, Vissink A, Kallenberg CG, Bootsma H (2009) Treatment of primary Sjogren syndrome with rituximab: extended follow-up, safety and efficacy of retreatment. Ann Rheum Dis 68:284–285

    Article  PubMed  CAS  Google Scholar 

  172. Ahmadi-Simab K, Lamprecht P, Nolle B, Ai M, Gross WL (2005) Successful treatment of refractory anterior scleritis in primary Sjogren's syndrome with rituximab. Ann Rheum Dis 64:1087–1088

    Article  PubMed  CAS  Google Scholar 

  173. Freidlin J, Wong IG, Acharya N (2007) Rituximab treatment for peripheral ulcerative keratitis associated with Wegener's granulomatosis. Br J Ophthalmol 91:1414

    Article  PubMed  Google Scholar 

  174. Zapata LF, Agudelo LM, Paulo JD, Pineda R (2007) Sjogren keratoconjunctivitis sicca treated with rituximab. Cornea 26:886–887

    Article  PubMed  Google Scholar 

  175. Cheung CM, Murray PI, Savage CO (2005) Successful treatment of Wegener's granulomatosis associated scleritis with rituximab. Br J Ophthalmol 89:1542

    Article  PubMed  CAS  Google Scholar 

  176. Onal S, Kazokoglu H, Koc A, Yavuz S (2008) Rituximab for remission induction in a patient with relapsing necrotizing scleritis associated with limited Wegener's granulomatosis. Ocul Immunol Inflamm 16:230–232

    Article  PubMed  CAS  Google Scholar 

  177. Taylor SR, Salama AD, Joshi L, Pusey CD, Lightman SL (2009) Rituximab is effective in the treatment of refractory ophthalmic Wegener's granulomatosis. Arthritis Rheum 60:1540–1547

    Article  PubMed  Google Scholar 

  178. Kurz PA, Suhler EB, Choi D, Rosenbaum JT (2009) Rituximab for treatment of ocular inflammatory disease: a series of four cases. Br J Ophthalmol 93:546–548

    Article  PubMed  CAS  Google Scholar 

  179. Tappeiner C, Heinz C, Specker C, Heiligenhaus A (2007) Rituximab as a treatment option for refractory endogenous anterior uveitis. Ophthalmic Res 39:184–186

    Article  PubMed  CAS  Google Scholar 

  180. Plskova J, Greiner K, Muckersie E, Duncan L, Forrester JV (2006) Interferon-alpha: a key factor in autoimmune disease? Invest Ophthalmol Vis Sci 47:3946–3950

    Article  PubMed  Google Scholar 

  181. Wilson SB, Kent SC, Patton KT, Orban T, Jackson RA, Exley M, Porcelli S, Schatz DA, Atkinson MA, Balk SP, Strominger JL, Hafler DA (1998) Extreme Th1 bias of invariant Valpha24JalphaQ T cells in type 1 diabetes. Nature 391:177–181

    Article  PubMed  CAS  Google Scholar 

  182. Taniguchi M, Harada M, Kojo S, Nakayama T, Wakao H (2003) The regulatory role of Valpha14 NKT cells in innate and acquired immune response. Annu Rev Immunol 21:483–513

    Article  PubMed  CAS  Google Scholar 

  183. Saito H, Ebinuma H, Satoh I, Miyaguchi S, Tada S, Iwabuchi N, Kumagai N, Tsuchimoto K, Morizane T, Ishii H (2000) Immunological and virological predictors of outcome during interferon-alpha therapy of chronic hepatitis C. J Viral Hepat 7:64–74

    Article  PubMed  CAS  Google Scholar 

  184. Okanoue T, Sakamoto S, Itoh Y, Minami M, Yasui K, Sakamoto M, Nishioji K, Katagishi T, Nakagawa Y, Tada H, Sawa Y, Mizuno M, Kagawa K, Kashima K (1996) Side effects of high-dose interferon therapy for chronic hepatitis C. J Hepatol 25:283–291

    Article  PubMed  CAS  Google Scholar 

  185. Tomer Y, Blackard JT, Akeno N (2007) Interferon alpha treatment and thyroid dysfunction. Endocrinol Metab Clin North Am 36:1051–1066

    Article  PubMed  CAS  Google Scholar 

  186. Felger JC, Alagbe O, Hu F, Mook D, Freeman AA, Sanchez MM, Kalin NH, Ratti E, Nemeroff CB, Miller AH (2007) Effects of interferon-alpha on rhesus monkeys: a nonhuman primate model of cytokine-induced depression. Biol Psychiatry 62:1324–1333

    Article  PubMed  CAS  Google Scholar 

  187. Kotter I, Zierhut M, Eckstein AK, Vonthein R, Ness T, Gunaydin I, Grimbacher B, Blaschke S, Meyer Riemann W, Peter HH, Stubiger N (2003) Human recombinant interferon alfa-2a for the treatment of Behcet's disease with sight threatening posterior or panuveitis. Br J Ophthalmol 87:423–431

    Article  PubMed  CAS  Google Scholar 

  188. Bodaghi B, Gendron G, Wechsler B, Terrada C, Cassoux N, du Huong LT, Lemaitre C, Fradeau C, LeHoang P, Piette JC (2007) Efficacy of interferon alpha in the treatment of refractory and sight threatening uveitis: a retrospective monocentric study of 45 patients. Br J Ophthalmol 91:335–339

    Article  PubMed  Google Scholar 

  189. Plskova J, Greiner K, Forrester JV (2007) Interferon-alpha as an effective treatment for noninfectious posterior uveitis and panuveitis. Am J Ophthalmol 144:55–61

    Article  PubMed  CAS  Google Scholar 

  190. Yang DS, Taylor SR, Lightman SL (2008) Interferon-alpha in the management of patients with Behcet's disease. Br J Hosp Med (Lond) 69:575–579

    Google Scholar 

  191. Gueudry J, Wechsler B, Terrada C, Gendron G, Cassoux N, Fardeau C, Lehoang P, Piette JC, Bodaghi B (2008) Long-term efficacy and safety of low-dose interferon alpha2a therapy in severe uveitis associated with Behcet disease. Am J Ophthalmol 146:837–844

    Article  PubMed  CAS  Google Scholar 

  192. Deuter CME, Kotter I, Gunaydin I, Stubiger N, Doycheva DG, Zierhut M (2009) Efficacy and tolerability of interferon alpha treatment in patients with chronic cystoid macular oedema due to non-infectious uveitis. Br J Ophthalmol 93:906–913

    Article  PubMed  CAS  Google Scholar 

  193. Guillaume-Czitrom S, Berger C, Pajot C, Bodaghi B, Wechsler B, Kone-Paut I (2007) Efficacy and safety of interferon-alpha in the treatment of corticodependent uveitis of paediatric Behcet's disease. Rheumatology (Oxford) 46:1570–1573

    Article  CAS  Google Scholar 

  194. Touitou V, Sene D, Fardeau C, Boutin T-H-D, Duhaut P, Piette J-C, LeHoang P, Cacoub P, Bodaghi B (2007) Interferon-alpha2a and Vogt-Koyanagi-Harada disease: a double-edged sword? Int Ophthalmol 27:211–215

    Article  PubMed  Google Scholar 

  195. Dick AD, Meyer P, James T, Forrester JV, Hale G, Waldmann H, Isaacs JD (2000) Campath-1H therapy in refractory ocular inflammatory disease. Br J Ophthalmol 84:107–109

    Article  PubMed  CAS  Google Scholar 

  196. Lockwood CM, Hale G, Waldman H, Jayne DR (2003) Remission induction in Behcet's disease following lymphocyte depletion by the anti-CD52 antibody CAMPATH 1-H. Rheumatology (Oxford) 42:1539–1544

    Article  CAS  Google Scholar 

  197. Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK (2008) Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 359:1786–1801

    Article  PubMed  Google Scholar 

  198. Jones JL, Coles AJ (2009) Spotlight on alemtuzumab. Int MS J 16:77–81

    PubMed  CAS  Google Scholar 

  199. Cortelezzi A, Pasquini MC, Gardellini A, Gianelli U, Bossi A, Reda G, Sarina B, Musto P, Barcellini W, Neri A, Deliliers GL (2009) Low-dose subcutaneous alemtuzumab in refractory chronic lymphocytic leukaemia (CLL): results of a prospective, single-arm multicentre study. Leukemia 23:2027–2033

    Article  PubMed  CAS  Google Scholar 

  200. Carroll HP, Paunovic V, Gadina M (2008) Signalling, inflammation and arthritis: Crossed signals: the role of interleukin-15 and -18 in autoimmunity. Rheumatology (Oxford) 47:1269–1277

    Article  CAS  Google Scholar 

  201. Curnow SJ, Pryce K, Modi N, Knight B, Graham EM, Stewart JE, Fortune F, Stanford MR, Murray PI, Wallace GR (2008) Serum cytokine profiles in Behcet's disease: is there a role for IL-15 in pathogenesis? Immunol Lett 121:7–12

    Article  PubMed  CAS  Google Scholar 

  202. Baslund B, Tvede N, Danneskiold-Samsoe B, Larsson P, Panayi G, Petersen J, Petersen LJ, Beurskens FJ, Schuurman J, van de Winkel JG, Parren PW, Gracie JA, Jongbloed S, Liew FY, McInnes IB (2005) Targeting interleukin-15 in patients with rheumatoid arthritis: a proof-of-concept study. Arthritis Rheum 52:2686–2692

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Ophthalmology at St. Franziskus Hospital, University Duisburg–Essen, Hohenzollernring 74, 48145, Muenster, Germany

    Arnd Heiligenhaus & Maren Hennig

  2. Section of Immunobiology, Department of Ophthalmology, Clinic of the University of Munich, Munich, Germany

    Stephan Thurau & Gerhild Wildner

  3. Department of Ophthalmology, University of Cologne, Cologne, Germany

    Rafael S. Grajewski

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  1. Arnd Heiligenhaus
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Heiligenhaus, A., Thurau, S., Hennig, M. et al. Anti-inflammatory treatment of uveitis with biologicals: new treatment options that reflect pathogenetic knowledge of the disease. Graefes Arch Clin Exp Ophthalmol 248, 1531–1551 (2010). https://doi.org/10.1007/s00417-010-1485-8

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  • DOI: https://doi.org/10.1007/s00417-010-1485-8

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