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IL-6-like cytokines and cancer cachexia

Consequences of chronic inflammation

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Abstract

An estimated 30% of cancer deaths are attributed to cachexia and its consequences. Cachexia (wasting syndrome) is the hypercatabolism of the body's carbon sources, proteins and lipids, for conversion into energy. It is induced by a variety of pathological conditions, including cancer. Among the inflammatory responses to cancer is the synthesis of cytokines, including IL-6 and related cytokines. These cytokines have been found to induce cach exia by altering metabolism of lipids and proteins. IL-6-like cytokines have been found to inhibit lipid biosynthesis by adipocytes, which increased the rate of lipid catabolism. Others have described the atrophy and increased catabolism of muscle protein due to IL-6. A cytokine closely-related to IL-6 is leptin, which plays a major role in lipid metabolism under normal conditions. The role of leptin in pathological conditions such as cancer cachexia has not yet been fully elucidated. Detailed mechanistic information about the induction of cancer cachexia by IL-6-like cytokines requires more research.

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References

  1. Brennan MF: Uncomplicatedstarvation versus cancer cachexia. Cancer Res. 1977;37:2359–2364.

    PubMed  CAS  Google Scholar 

  2. Merkel M, Weinstock PH, Chajek-Shaul T, Radner H, Yin B, Breslow JL, Goldberg IJ: Lipoprotein lipase expression exclusively in the liver. J Clin Invest 1998;102:893–901.

    PubMed  CAS  Google Scholar 

  3. Lehninger A: Organ interrelationships in the metabilism of mammals. In Biochemistry, 1975; 829–845, New York: Worth.

    Google Scholar 

  4. Martin F, Santolaria F, Batista N, et al.: Cytokine levels (IL-6 and IFN-g), acute phase response and nutritional statuas prognostic factors in lung cancer. Cytokine 1999;11:80–86.

    Article  PubMed  CAS  Google Scholar 

  5. Espat NJ: Cliary neurotrophic factor is catabolic and shares with IL-6 the capacity to induce anacute phase response. Am J Physiol 1996;271:R185-R190.

    PubMed  CAS  Google Scholar 

  6. Janik JE, Curti BD, Considine RV, et al.: Interleukin la increases serum leptin concentrations in humans. J Clin Endocrinol Met 1997;82:3084–3086.

    Article  CAS  Google Scholar 

  7. Oldenburg HSA, Rogy MA, Lazarus DD, et al.: Cachexia, and the acute-phase response in inflammation are regulated by interleukin-6. Eur J Immunol 1993;23:1889–1894.

    Article  PubMed  CAS  Google Scholar 

  8. Haumann H, Richards C, Gauldie J: Interaction among hepatocytestimulating factors, interleukin 1, and glucocorticoids for regulation of acute phase plasma proteins in human hepatoma (HepG2) cells. J Immunol 1987;139:4122–4128.

    Google Scholar 

  9. Baumann H, Onorato V, Gauldie J, Jahreis GP: Distinct sets of acute phase plasma proteins are stimulated by separate human hepatocyte-stimulating factors and monokines in rat hepatoma cells. J Biol Chem 1987;262:9756–9768.

    PubMed  CAS  Google Scholar 

  10. Andus T, Geiger T, Hirano T, Kishimoto T, Heinrich PC: Action of recombinant human interleukin 6, interleukin 1b and tumor necrosis factor a on the mRNA induction of acute-phase proteins. Eur J Immunol 1988;18:739–746.

    Article  PubMed  CAS  Google Scholar 

  11. Marinkovic S, Jahreis GP, Wong GG, Baumann H: IL-6 modulates the synthesis of a specific set of acute phase plasma proteins in vivo. J Immunol 1989;142:808–812.

    PubMed  CAS  Google Scholar 

  12. Moshage HJ, Roelofs HMJ, vsn Pelt JF, et al.: The effect of interleukin-1, interleukin-6 and its interrelationship on the synthesis of serum amy loid A and c-reactive protein in primary cultures of adulthuman hepatocytes. Biochem Biophys Res. Comm 1988;155:112–117.

    Article  PubMed  CAS  Google Scholar 

  13. Kaibara A, Espat NJ, Auffenberg T, et al.: Interle ukin 6, but not ciliary neurotrophic factor or leukemia inhibiitory factor, is responsible for the acute phase response to turpentine-induced myositis. Cytokine. 1998;10: 452–456

    Article  PubMed  CAS  Google Scholar 

  14. Beutler B, Cerami A: The common mediator of shock, cachexia, and tumor necrosis. Adv Immunol 1988;42:213–231.

    PubMed  CAS  Google Scholar 

  15. Beutler B, Cerami A: Tumornecrosis, cachexia, shock, and inflammation: A common mediator. Ann Rev Biochem 1988;57:505–518.

    Article  PubMed  CAS  Google Scholar 

  16. Truyens C: The cachexia associated with Trypanosomacruziacute infection in mice is attenuated by anti-TNF-alpha, but not by anti-IL-6 oranti-IFN-gamma antibodies. Parasite Immunol 1995;17:561–568.

    PubMed  CAS  Google Scholar 

  17. Oliff A, Defeo-Jones D, Boyer M, et al.: Tumors secreting TNF/cachectininduce cachexia in mice. Cell 1987;80:555–563.

    Article  Google Scholar 

  18. Sonti G, Ilyin SE, Plata-Salaman CR: Neuropeptide Y blocks and reverses interleukin-1b-induced anorexia in rats. Peptides 1996; 17:517–520.

    Article  PubMed  CAS  Google Scholar 

  19. Strassman G, Masui Y, Chizzonite R, Fong M: Mechanisms of experimental cancer cachexia. Local involvement of IL-1 in Colon-26 tumor. J Immunol 1993d;150:2341–2345.

    Google Scholar 

  20. Beutler B, Mahoney J, Le Trang N, Pekala P, Cerami A: Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264. 7 cells. J Exp Med 1985; 161:984–995.

    Article  PubMed  CAS  Google Scholar 

  21. Cryer A: Tissue lipoprotein lipase activity and its action in lipoprotein metabolism. Int J Biochem 1981;13:525–541.

    Article  PubMed  CAS  Google Scholar 

  22. Garcia-Martinez C: Is TNF really involved in cancer cachexia? Cancer Invest 1997;15:47–54.

    PubMed  CAS  Google Scholar 

  23. Strassman G, Fong M, Kenney JS, Jacob CO: Evidence for the involvement of interleukin 6 in experimental cancer cachexia. J Clin Invest 1992;89:1681–1684.

    Google Scholar 

  24. Aarden L, Lansdorp P, De Groot E: A grow thfactor for B cell hybridomas produced by human monocytes. Lymphokines 1985;10:175–185.

    CAS  Google Scholar 

  25. Aarden L, De Groot E, Schaap OL, Lansdorp P: Production of hybridoma grow thfactorby human monocytes. Eur J Immunol 1987;17:1411–1416.

    Article  PubMed  CAS  Google Scholar 

  26. Aarden LA: Hybridoma growth factor. Ann NY Acad Sci 1989; 557:192–199.

    PubMed  CAS  Google Scholar 

  27. Brakenhoff JPJ, de Groot ER, Evers RF, Pannekoek H, Aarden LA: Molecularcloning and expression of hybridoma growth factor in Escherichia coli. J Immunol 1987;139:4116–4121.

    PubMed  CAS  Google Scholar 

  28. Coulie PG, Cayphas S, Vink A, Uyttenbove C, Van Snick J: Interleukin-HPI-related hybridoma and plas macytoma growth factors induced by lipopolysaccharide in vivo. European Journal of Immunology 1987;17:1217–1220.

    Article  PubMed  CAS  Google Scholar 

  29. Van Damme J, Van Beeumen J, Decock B, Van Snick J, De Ley M, Billiau A: Separation and comparsion of two monokines with lymphocyte-activating factor activity: IL-1bandhybridoma growth factor (HGF). J Immunol 1988;140:1534–1541.

    PubMed  Google Scholar 

  30. Van Damme J, Opdenakker G, Simpson RJ, et al.: Identification of the human 26 kD protein, interferon β2 (IFN-β2) as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor. J Exp Med 1987;165:914–921.

    Article  PubMed  Google Scholar 

  31. Ramadori G, Van Damme J, Rieder H, Meyerzum Buschenfelde K-H: Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic proteinsyn thesis in human and mouse. Comparison with interleukin 1b and tumor necrosis factor-a. Eur J Immunol 1988;18:1259–1264.

    Article  PubMed  CAS  Google Scholar 

  32. Schooltink H, Stoyan T, Lenz D, et al.: Structural and functional studies on the human hepatic interleukin-6-receptor. Biochem J 1991;277:659–644.

    PubMed  CAS  Google Scholar 

  33. Sehgal PB: Interleukin 6: a regulator of plasma protein gene expression in hepatic and nonhepatic tissues. Mol Biol Med 1990;7:117–130.

    PubMed  CAS  Google Scholar 

  34. Zuraw BL, Lotz M: Regulation of the hepatic synthesis of C1 inhibitory by the hepatocyte stimulating factors interleukin 6 and interferon 7. J Biol Chem 1990; 265:12664–12670.

    PubMed  CAS  Google Scholar 

  35. Castell JV, Geiger T, Gross V, et al. Plasma clearance, organ distribution and target cells of interleukin-6/hepatocyte-stimulating factor in the rat. Eur J Biochem 1988;177:357–361.

    Article  PubMed  CAS  Google Scholar 

  36. Frei K, Leist TP, Meager A, et al.: Production of B Cell Stimulatory Factor-2 and Interferon γ in the Central Nervous system during Viral meningitis and Encephalitis. Journal of Experimental Medicine. 1988;168:449–453.

    Article  PubMed  CAS  Google Scholar 

  37. Hahn T, Shulma L, Karov Y, Vorst E, Berrebi A: Involvementofinterleukin-6 in the autocrine stimulation of chronic lymphocytic leukemia B cells by tumor necrosis factor. Leuk Lymph 1991;5:65–69.

    Google Scholar 

  38. Hirano T, Taga T, Yasukawa K, et al.: Human B cell differentiation factor defined by an anti-peptide antibody and its possible role in autoantibody production. Proc Natl Acad Sci USA 1987;84:228–231.

    Article  PubMed  CAS  Google Scholar 

  39. Hirano T, Matsuda T, Tumer M, et al.: Exdessive Production of Interleukin 6/B Cell Stimulatory Factor-2 in Rheumatoid Arthritis. European Journal of Immunology 1988;18:1797–1801.

    Article  PubMed  CAS  Google Scholar 

  40. Helfgott DC, Tatter SB, Santhanam U, et al.: Muftiple Forms of IFN-β/IL-6 in Serum and Body Fluids during A cute Bacterial Infection. Journal of Immunology 1989;142:948–953.

    CAS  Google Scholar 

  41. May LT, Santhanam U, Tatter SB, Ghrayneb J, Sehgal PB: Multiple forms of human IL-6. Ann NY Acad Sci 1989;557:114–119.

    PubMed  CAS  Google Scholar 

  42. Baumann H, Schendel P: Interleukin-11 regulates the hepatic expression of the same plasma prole in genes as interleukin-6. J Biol Chem 1991;266:20424–20427

    PubMed  CAS  Google Scholar 

  43. Yin T, Schendel P, Yang Y-C: Enhancement of in vitro and in vivo antigen-specific antibody responses by interleukin 11. J Exp Med 1992;175:211–216.

    Article  PubMed  CAS  Google Scholar 

  44. Alexander HR, Wong GH, Doherty GM, Vanzon DJ, Fraker DL, Norton JA: Differentiation factor/leukemia inhibitory factor protection against le thal endotoximia in mice: Synergistic effect with interleukin 1 and tumornecrosis factor. J Exp Med 1992;175:1139–1142.

    Article  PubMed  CAS  Google Scholar 

  45. Baumann H, Wong GG: Hepatocyte-stimulating factor III share structural and functional identity with leukemia-inhibitory factor. J Immunol 1989;143:1163–1167.

    PubMed  CAS  Google Scholar 

  46. Yoshimura A, Ichihara M, Kinjyo I, et al.: Mcuse oncostatin M: an immediate early gene induced by multiple cytokines through the JAK-STAT5 pathway. EMBO J 1996:15:1055–1063.

    PubMed  CAS  Google Scholar 

  47. Lam A, Fuller F, Miller J, et al.: Sequence and structural organization of the human gene encoding ciliary neurotrophic factor. Gene 1991;192:271–276.

    Article  Google Scholar 

  48. Negro A, Tolosano E, Skaper SD, et al.: Cloning and expression of human ciliary neurotrophic factor. Eur J Biochem 1991;201:289–294.

    Article  PubMed  CAS  Google Scholar 

  49. Wollert KC, Chien KR: Cardiotrophin-1 and the role of gpl 30-dependent signaling pathways in cardiac growth and development. J Mol Med 1997;75:492–501.

    Article  PubMed  CAS  Google Scholar 

  50. Senaldi G, Vamum BC, Sarmiento U, et al. Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family. Proc Natl Acad Sci USA 1999;96:11458–11463.

    Article  PubMed  CAS  Google Scholar 

  51. Taga T, Hibi M, Hirata Y, et al.: Interleukin-6 triggers the association of its receptor with apossible signal transducer, gpl 30. Cell 1989;58:573–581.

    Article  PubMed  CAS  Google Scholar 

  52. Kishimoto T, Akira S, Taga T: IL-6 receptor and mechanism of signal transduction. Int J Immunol 1992;14:431–438.

    Article  CAS  Google Scholar 

  53. Narazaki M, Withuhn BA, Yoshida K, et al.: Activation of JAK 2 kinase mediated by the interleukin 6 signal transducer gpl 30. Proc Natl Acad Sci USA 1994;91:2285–2289.

    Article  PubMed  CAS  Google Scholar 

  54. Stahl N, Houlton TG, Farruggella T, et al.: Association andactivation of Jak-Tyk kinases by CNTF-LIFOSM-IL-6 breceptorcomponents. Science 1994;263:92–96.

    Article  PubMed  CAS  Google Scholar 

  55. Kiuchi N, Nakajima K, Ichiba M, et al.: STAT 3 is required for the gpl 30-mediated full activation of the c-myc gene. J Exp Med 1999; 189:63–73.

    Article  PubMed  CAS  Google Scholar 

  56. Alonzi T, Fattori E, Cappelletti M, Ciliberto G, Poli V: Impaired STAT3 activation followinglocalized inflam matory stimulus in IL-6-deficient mice. Cytokine 1998;10:13–18.

    Article  PubMed  CAS  Google Scholar 

  57. Baumann H, Strassmann G: Suramininhibits the stimulation of acute phase protein genes by IL-6-type cytokines in rat hepatoma cells. J Immunol 1993; 151:1456–1462.

    PubMed  CAS  Google Scholar 

  58. Chen-Kiang S, Hsu W, Natkuman Y, zhang X: Nuclearsignallingby interleukin-6. Curr Opin Immunol 1993;5:124–128.

    Article  PubMed  CAS  Google Scholar 

  59. Akira S, Isshiki H, Nakajima T, et al.: A Nuclear Factor for the IL-6 Gene (NF-IL6). Interleukins: Molecular Biology and Immunology, ed. T. Kishimoto, 1992;51: Basel: Kargel.

    Google Scholar 

  60. Rose TM, Bruce AG: Oncostatin M isamemberofa family that includes leukemia-inhibitory factor, gronulocyte colony-stimulating factor, and interleukin 6. Proc Natl Acad Sci USA 1991;88:8641–8645.

    Article  PubMed  CAS  Google Scholar 

  61. Richards CD, Kerr C, Tanaka M, et al.: Regulation of tussue of metalloproteinase-1 in fibroblasts and acute phase proteins in hepatocytes in vitro by mouse oncostatin M, cardiotrophi-1, and IL-6. J Immunol 1997;159:2431–2437.

    PubMed  CAS  Google Scholar 

  62. Yin T, Taga T, Tsang ML-S, Yasukawa K, Kishimoto T, Yang Y-C. Involvement of IL-6 signal transducer gpl 30 in IL-11-mediated signal transduction. J Immunol 1993;151:2555–2561.

    PubMed  CAS  Google Scholar 

  63. Fourcin M, Chevalier S, Lebrun J-J, et al.: Involvement of gpl 30/interleukin-6 receptortransducing component in interleukin-11 receptor. Eur J Immunol 1994;24: 277–280.

    Article  PubMed  CAS  Google Scholar 

  64. Barton BE, Jackson JV, Lee F, Wagner J: Oncostatin M stimulates proliferation in B9 hybridoma cells: potential role of oncostatin M in plasmacytoma development. Cytokine 1994;6:147–153.

    Article  PubMed  CAS  Google Scholar 

  65. Gearing DP, Comeau MR, Friend DJ, et al.: The IL-6 signal transducer, gpl 30: An oncostatin M receptor and affinity converter for the LIF receptor. Science 1992; 255:1434–1437.

    Article  PubMed  CAS  Google Scholar 

  66. Barlon BE, Jakway JP, Smith SR, Siegel MI: Cytokine inhibition by a novel steroid, mometasone furoate. Immunopharm Immunotox 1991;13:251–262.

    Google Scholar 

  67. Bauer J, Ganter U, Geiger T, et al.: Regulation of interleukin-6 expression in cultured human blood monocytes and monocyte-derived macrophages. Blood 1988;72:1134–1140.

    PubMed  CAS  Google Scholar 

  68. Billiar TR, Curran RD, Williams DL, Kispert PH: Liver nonparenchymal cells are stimulated to provide interleukin 6 for induction of the hepatic acute-phase response in endotoxemiabutnot in remote local ized inflammation. Arch Surg 1992;127:31–37.

    PubMed  CAS  Google Scholar 

  69. Bitterman H, Kinarty A, Lazarovich H, Lehat N: Acute release of cytokines is proportional to tissue injury induced by surgical trauma and shock in rats. J Clin Immunol 1991;11:184–192.

    Article  PubMed  CAS  Google Scholar 

  70. Barton BE: IL-6: Thsights into novel biological activities. Clin Immunol Immunopath 1997;85:16–20.

    Article  CAS  Google Scholar 

  71. Miles SA, Rezai AR, SalazarGonzalez JF, et al.: AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6. Proc Natl Acad Sci USA 1990;87:4068–4072.

    Article  PubMed  CAS  Google Scholar 

  72. Brown TJ, Rowe JM, Liu J, Shoyab M: Regulation of IL-6 expression by oncostatin M. J Immunol 1991a;147:2175–2180.

    PubMed  CAS  Google Scholar 

  73. Barton BE, Jackson JV: The protective role of IL-6 inasepticshock model. Infect Immun 1993;61:1496–1499.

    PubMed  CAS  Google Scholar 

  74. Chen W, Havell EA, Gigliotti F, Harmsten AG: Interleukin-6 production in a murine model of Pneumocystise carinii pneumonia: relation to resistance and inflammatory response. Infect Immun 1993;61:97–102.

    PubMed  CAS  Google Scholar 

  75. Barton BE: Effect of interleukin-6 in septic shock. Drug News & Perspectives 1993;6:641–646.

    Google Scholar 

  76. Barton BE, Finkelman FD: Anti-inflammatory cytokines. Agents & Actions 1993;39:R1-R3.

    Article  Google Scholar 

  77. Barton BE, Shortall J, Jackson JV: Interleukins 6 and 11 protect mice from mortality in astaphylococcal enterotoxin-induced toxic shock model. Infect Immun 1996;64: 714–718.

    PubMed  CAS  Google Scholar 

  78. Heremans H, Dillen C, Put W, Van Damme J, Billiau A: Protective effect of anti-interleukin (IL)-6 antibody against endotoxin, associated with paradoxically increased IL-6 levels. Eur J Immunol 1992;22:2395–2401.

    Article  PubMed  CAS  Google Scholar 

  79. Mihara M, Ikuta M, Koishihara Y, Ohsugi Y: Interleukin 6 inhibits delayed-type hypersensitivity and the development of adjuvant arthritis. Eur J Immunol 1991;21: 2327–2331.

    Article  PubMed  CAS  Google Scholar 

  80. Aderka D, Le J, Vilcek J: IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice. J Immunol 1989;143:3517–3523.

    PubMed  CAS  Google Scholar 

  81. Aderka D, Maor Y, Novick D, et al.: Interleukin-6 inhibits the proliferation of B-chronic lymphocytic leukemia cells that is induced by tumor necrosis factor-a. Blood 1993;81:2076–2084.

    PubMed  CAS  Google Scholar 

  82. Bermudez LE, Wu M, Petrofsky M, Young LS: Interleukin-6 antagonizes tumor necrosis factor-mediated mycobacteriostatic and mycobactericidal activities in macrophages. Infect Immun 1992; 60:4245–4252.

    PubMed  CAS  Google Scholar 

  83. Leng SX, Elias JA: Interleukin-11 inhibits macrophage interleukin-12 production. J Immunol 1997;159: 2161–2168.

    PubMed  CAS  Google Scholar 

  84. Castell JV, Andus T, Kunz D, Heinrich PC: Interleukin-6. The major regulator of acute-phase protein synthesis in man and rat. Ann NY Acad Sci 1989;557:87.

    PubMed  CAS  Google Scholar 

  85. Kordula T, Rokita H, Koj A, Fiers W, Gauldie J, Baumann H: Effects of interleukin-6 and leukemia inhibitory factor on the acute phase response and DNA synthesis in cultured rat hepatocytes. Lymph Cyto Res 1991;10:23–26.

    CAS  Google Scholar 

  86. Jin H, Yang R, Keller GA, et al.: In vivo effects of cardiotrophin-1. Cytokine 1996;8:920–926.

    Article  PubMed  CAS  Google Scholar 

  87. Fantuzzi G, Benigni F, Sironi M, et al.: Cihary neurotrophic factor (CNTF) induces serum amyloid A, hypoglycemia and anorexia, and potentiates IL-1 induced corticosterone and IL-6 production in mice. Cytokine 1995;7:150–156.

    Article  PubMed  CAS  Google Scholar 

  88. Marshall MK, Doerrler W, Feingold KR, Grunfeld C: Leukemia inhibitory factor induces changes in lipid metabolism in cultured adipocytes. Endocrinol 1994;135: 141–147.

    Article  CAS  Google Scholar 

  89. Hirano T: Interleukin 6 (IL-6) and its receptor: Their role in plasma cell neoplasias. Int J Cell Clon 1991;9:166–184.

    CAS  Google Scholar 

  90. Jourdan M, Zhang XG, Portier M, Boiron J-M, Bataille R, Klein B: IFN-α induces autocrine production of IL-6 in myeloma cell lines. J Immunol 1991;147:4402–4407.

    PubMed  CAS  Google Scholar 

  91. Juge-Morineau N, Francois S, Puthier D, Godard A, Bataille R, Amiot M: The gp130 family cytokines IL-6, LIF and OSM but not IL-11 can reverse the antiproliferative effect of dexamethasone on human myeloma cells. Br J Hematol 1995;90:707–710.

    CAS  Google Scholar 

  92. Klein B, Zhang XG, Jourdain M, et al.: Interleukin-6 is the central tumor growth factor in vitro and in vivo in multiple myeloma. Eur Cytokine Net 1990;1:193

    CAS  Google Scholar 

  93. Schwab G, Siegall C, Aarden L, Neckers L, Nordan R: Identification of an IL-6-modulated autocrine growth loop in a human multiple myeloma cell line. Proc Am Assoc Cancer Res 1990;31:243

    Google Scholar 

  94. Barton BE, Murphy TF: Constitutive expression of IL-6-like cytokines in normal bone marrow: Implications for myeloma pathophysiology. Cytokine 2000;12: 18–27.

    Article  CAS  Google Scholar 

  95. Brandt SJ, Bodine DM, Dunbar CE, Nienhuis AW: Dysregulated interleukin 6 expression produces a syndrome resembling Castleman's disease in mice. J Clin Invest 1990;86:592–599.

    PubMed  CAS  Google Scholar 

  96. Yoshizaki K, Matsuda T, Kaieda T, et al.: Pathological significance of interleukin 6 (IL-6/B SF-2) in Castleman's disease. Blood 1989;74:1360–1367.

    PubMed  CAS  Google Scholar 

  97. Jourdan M, Bataille R, Seguin J, Zhang X-G, Chaptal RA, Klein B: Constitive production of interleukin-6 and immunologic features in cardiac myxoma. Arthr Rheum 1990;33:398–402.

    Article  CAS  Google Scholar 

  98. Fugger L, Morling N, Bendtzen K, et al.: IL-6 gene polymorphism in rheumatoid arhtirits, pauciarticular juvenile rheumatoid arthritis, systemic lupus erythematosus, and in healthy Danes. Journal of Immunogenetics 1990;16:461–465.

    Article  Google Scholar 

  99. Hirohata S, Miyamoto T: Elevated levels of interleukin-6 in cerebrospinal fluid from patients with systemic lupus erythematosus and central nervous system involvement. Arthr Rheum 1990;33: 644–649.

    Article  CAS  Google Scholar 

  100. Kitani A, Hara M, Hirose T, et al.: Aulostimulatory 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 1992;88:75–83.

    PubMed  CAS  Google Scholar 

  101. Linker-Israeli M, Deans RJ, Wallace DJ, Prehn J, Ozeri-Chen T, Klinenberg JR: Elevated levels of endogenous IL-6 in systemic lupus erythematosus. A putative role in pathogenesis. J Immunol 1991; 147:117–123.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  103. Pelton BK, Hylton W, Denman AM. Activation of IL-6 production by UV irradiation of blood mononuclear cells from patients with systemic lupus erythematosus. Clin Exp Immunol 1992;89:251–254.

    PubMed  CAS  Google Scholar 

  104. Swaak A, van Rooyen A, Aarden LA: Interleukin-6 (IL-6) andacute phase proteins in the disease course of patients with systemic lupus erythematosus. Rheumatol Int 1989; 8:263–268.

    Article  PubMed  CAS  Google Scholar 

  105. Warrington RJ, Rutherford WJ: Normal mitogen-induced suppression of the interleukin-6 (IL-6) response and its deficiency in systemic lupus erythematosus. J Clin Immunol 1990;10:52–60.

    Article  PubMed  CAS  Google Scholar 

  106. Starnes Jr. HF, Warren RS, Jeevanandam M, et al.: Tumor necrosis factor and the acute metabolic response to tissue injury in man. J Clin Invest 1988;82: 1321–1325.

    PubMed  CAS  Google Scholar 

  107. Ling PR: Mechanisms of host wasting induced by administration of cytokines in rats. Am J Physiol 1997;272:E333-E339.

    PubMed  CAS  Google Scholar 

  108. Luheshi GN, Gardner JD, Rushforth DA, Loudon AS, Rothwell NJ: Leptin actions on food intake and body temperature mediated by IL-1. Proc Natl Acad Sci USA 1999;96:7047–7052.

    Article  PubMed  CAS  Google Scholar 

  109. Bellido T, Stahl N, Farrugella TJ, Borba V, Yancopoulos GD, Manolagas SC: Detection of receptors for interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in bone marrow stromal/osteo blastic cells. J Clin Invest 1996;97:431–437.

    PubMed  CAS  Google Scholar 

  110. Hermanns HM, Radtke S, Haan C, et al.: Contributions of leukemia inhibitory factor receptor and oncostatin M receptor to signal transduction in heterodimeric complexes with glycoprotein in 130. J Immunol 1999;163:6651–6658.

    PubMed  CAS  Google Scholar 

  111. Ip NY, Nye SH, Boulton TG, et al.: CNTF and LIF act on neuronal cells viashared signaling pathways that involve the IL-6 signal transducing receptor component gp130. Cell 1992;69:1121–1132.

    Article  PubMed  CAS  Google Scholar 

  112. Kurth I, Horsten U, Pflanz S, et al.: Activation of the signal transducer glycoprotein 130 by both IL-6 and IL-11 requires two distinct bindingepitopes. J Immunol 1999;162: 1480–1487.

    PubMed  CAS  Google Scholar 

  113. Mori M, Yamaguchi K, Honda S, et al.: Cancer cachexia syndrome developed innude mice bearingmelanoma cells producing leukemia-inhibitory factor. Cancer Res 1991; 51:6656–6659.

    PubMed  CAS  Google Scholar 

  114. Billingsley KG: Macro phage-derived tumor necrosis factor and tumor-derived leukemia inhibitory factor and interleukin-6: possible cellular mechanisms of cancer cachexia. Ann Surg Oncol 1996;3: 29–35.

    Article  PubMed  CAS  Google Scholar 

  115. Gloaguen I: Ciliary neurotrophic factorcorrects obesity and diabetes associated with leptin deficiency and resistance. Proc Natl Acad Sci USA 1997;94:6456–6461.

    Article  PubMed  CAS  Google Scholar 

  116. Henderson JT, Mullen BJM, Roder JC: Physiological effects of CNTF-induced wasting. Cytokine 1996;8: 784–793.

    Article  PubMed  CAS  Google Scholar 

  117. Martin D, Merkel E, Tucker KK, et al.: Cachectic effect of ciliary neurotrophic factor on innervated muscle. Am J Physiol 1996;271: R1422-R1428.

    PubMed  CAS  Google Scholar 

  118. Black K, Garrett IR, Mundy GR: Chinese hamster ovarian cells transfected with the murine interleukin-6 gene cause hypercalcemia as well as cachexia, leukocytosis and thrombocytosis in tumor-bearing nude mice. Endocrin 1991; 128:2657–2659.

    Article  CAS  Google Scholar 

  119. Gelin J, Moldawer LL, Lonroth C, et al.: Appearance of hybridoma growth factor/interleukin-6 in the serum of mice bearing a methyl-cholanthrene-induced sarcoma. Biochem Biophys Res Commun 1988;157:575–579.

    Article  PubMed  CAS  Google Scholar 

  120. Tamura S, Ouchi KF, Mori K, et al.: Involvement of human interleukin 6 in experimental cachexia induced by a human uterine cervical carcinoma xenograft. Clin Can Res 1995;1:1353–1358.

    CAS  Google Scholar 

  121. Tabibzadeh SS, Poubouridis D, May LT, Sehgal PB: Interleukin-6 immunoreactivity in human tumors. Am J Pathol 1989;135: 427–433.

    PubMed  CAS  Google Scholar 

  122. McIntosh JK, Jablors DM, Mule JJ, et al.: In vivo induction of IL-6 by administration of exogenouscytokines and detection of de novoserum levels of IL-6 in tumor-bearing mice. J Immunol 1989; 143:162–167.

    PubMed  CAS  Google Scholar 

  123. Barton BE, Cullison J, Jackson J, Murphy T: A model that reproduces syndromes associated with human multiple myeloma in non-irradiated SC1D mice. Proc Soc Exp Bio Med 2000;223:1–8.

    Article  Google Scholar 

  124. Cahlin C, Korner A, Axelsson H, Wang W, Lundholm K, Svanberg E: Experimental cancer cachexia: the role of host-derived interleukin (IL)-6, IL-12, interferon-γ, and tumor necrosis factor a evaluated in gene knockout, tumor-bearing mice on C57 BL background and eicosanoid-dependent cachexia. Cancer Res 2000;60:5488–5493.

    PubMed  CAS  Google Scholar 

  125. Molotkov A, Satoh M, Tohyama C: Tumor growth and food intake in interleukin-6 gene knock-out mice. Cancer Lett 1998;132:187–192.

    Article  PubMed  CAS  Google Scholar 

  126. Suematsu S, Matsuda T, Aozasa K, et al.: IgG1 plasmacytosis in interleukin 6 transgenic mice. Proceedings of the National Academy of Sciences, USA 1989;86: 7547–7551.

    Article  CAS  Google Scholar 

  127. De Benedetti F, Alonzi T, Moretta A, et al.: Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-1. J Clin Invest 1997;99:643–650.

    PubMed  Google Scholar 

  128. Fattori E, Lazzaro D, Musiani P, Modesti A, Alonzi T, Ciliberto G: IL-6 expression in neurons of transgenic mice causes reactive astrocytes and increase in ramified microglial cells but no neuronal damage. Eur J Neurosci 1995;7: 2441–2449.

    Article  PubMed  CAS  Google Scholar 

  129. Tsujinaka T, Ebisui C, Fujita J, et al.: Muscle undergoes atrophy in association with increase of lysosomal cathepsin activity in interleukin-6 transgenic mice. Biochem Biophys Res Commun 1995;207: 168–174.

    Article  PubMed  CAS  Google Scholar 

  130. Tsujinaka T, Fujita J, Ebisui C, et al.: Interleukin 6 receptorantibody inhibits muscle atrophy and modulates proteolytic systems in interleukin 6 transgenic mice. J Clin Invest 1996;97:244–249.

    PubMed  CAS  Google Scholar 

  131. Tisdale MJ: Protein Loss in cancer cachexia. Science 2000;289:2293–2294.

    Article  PubMed  CAS  Google Scholar 

  132. Fumamoto M, Fujio Y, Kunisada K: Signal transducer and activator of transcription 3 is required for glycoprotein 130-mediated induction of vascular endothelial growth factor in cardiac myocytes. J Biol Chem 2000;275:10561–10566.

    Article  Google Scholar 

  133. Fattori E, Della Rocca C, Giorgio M, Dente B, Pozzi L, Ciliberto G: Development of progressive kidney damage and myeloma kidney in interleukin-6 transgenic mice. Blood 1994;83:2570–2579.

    PubMed  CAS  Google Scholar 

  134. Suzuki SM, Jimi KA, Funakoshi A: Induction of acute pancreatitis by cerulein in human IL-6 gene transgenic mice. Pancreas 2000; 21:86–92.

    Article  PubMed  CAS  Google Scholar 

  135. Nelson TE, Campbell IL, Gruol DL: Altered physiology of Purkinje neurons in cerebellar slices from transgenic mice with chronic central nervous system expression of interleukin-6. Neuroscience 1999;89:127–136.

    Article  PubMed  CAS  Google Scholar 

  136. Ward NS, Waxman AB, Homer RJ, et al.: Interleukin-6-induced protection in hyperoxic acute lung injury. Am J Respir Cell Mol Biol 2000;22:535–542.

    PubMed  CAS  Google Scholar 

  137. Woodroofe C, Muller W, Ruther U: Long-term consequences of interleukin-6 overex pression in transgenic mice. DNA Cell Biol 1992;11:587–592.

    PubMed  CAS  Google Scholar 

  138. Bamber B, Reife RA, Haugen HS, Clegg CH: Oncostatin M stimulates excessive extracellular matrix accumulation in a transgenic mouse model of connective tissue disease. J Mol Med 1998;76: 61–69.

    Article  PubMed  CAS  Google Scholar 

  139. Kafsume A, Miyai T, Suzuki H, et al.: Interlukin-6 overex, pression cannot generate serious disorders in severe combined immunodeficient mice. Clin Immunol Immunopath 1997;82:117–124.

    Article  Google Scholar 

  140. Hirota H, Yoshida K, Kishimoto T, Taga T: Continuous activation of gpl 30, asignal-transducingreceptor component for interleukin 6-related cytokines, causes myocardial hypertrophy in mice. Proc Natl Acad Sci USA 1995; 92:4862–4866.

    Article  PubMed  CAS  Google Scholar 

  141. Dalrymple SA, Lucian LA, Slattery R, IL-6 deficient mice are highly susceptible to L. monocytoges infection: correlation with inefficient neutrophilia. Infect Immun 1995;63:2262–2268.

    PubMed  CAS  Google Scholar 

  142. Suzuki Y, Rani S, Liesenfeld O: Impaired resistance to the development of toxoplasmic encephalitis in interleukin-6-deficient mice. Infect Immun 1997;65:2339.

    PubMed  CAS  Google Scholar 

  143. Moskowitz NH, Brown DR, Reiner SL: Efficient immunity against Leishmania major in the absence of interleukin-6. Infect Immun 1997;65:2448–2450.

    PubMed  CAS  Google Scholar 

  144. Gallucci RM, Simeonova PP, Matheson JM, et al.: Impaired cutaneous wound healing in interleukin-6-deficient and immuno-suppressed mice. FASEB J 2000; 14:2525–2531.

    Article  PubMed  CAS  Google Scholar 

  145. Fattori E, Cappelletti M, Costa P, et al.: Defective inflammatory response in interleukin-6-deficient mice. J Exp Med 1994;180: 1243–1250.

    Article  PubMed  CAS  Google Scholar 

  146. Cuzzocrea S, De Sarro G, Constantino G, IL-6 knock-out mice exhibit resistance to splanchnic artery occlusion shock. J Leuko Biol 1999;66:471–480.

    PubMed  CAS  Google Scholar 

  147. Pestka JJ, Zhou HR: Interleukin-6-deficient mice refractory to IgA dysregulation but not anorexia induction by vomitoxin (deoxynivalenol) ingestion. Food Chem Toxicol 2000;38:565–575.

    Article  PubMed  CAS  Google Scholar 

  148. Kumanogoh A, Marukawa S, Kumanogoh T, et al.: Impairment of antigen-specific antibody production in transgenic mice expressing a dominant-negative form of gpl 30. Proc Natl Acad. Sci USA 1997;94:2478–2482.

    Article  PubMed  CAS  Google Scholar 

  149. Baumann H: The full-lengthleptin receptor has signaling capabilites of interleukin 6-type cytokine receptors. Proc Natl Acad Sci USA 1996;93:8374–8378.

    Article  PubMed  CAS  Google Scholar 

  150. Ghilardi N, Ziegler S, Wiestner A, Stoffel R, Heim MH, Skoda RC: Defective STAT signaling by the leptin receptor in diabetic mice. Proc Natl Acad Sci USA 1996;93:6231–6235.

    Article  PubMed  CAS  Google Scholar 

  151. Ghilardi N: The leptin receptor activates Janus kinase 2 and signals for proliferation in a factor-dependent cell line. Mol Endocrinol 1997;11:393–399.

    Article  PubMed  CAS  Google Scholar 

  152. Bado A, Levasseur S, Attoub S, et al.: The stomach is a source of leptin. Nature 1998;394:790–793.

    Article  PubMed  CAS  Google Scholar 

  153. Hoggard N, Hunter L, Duncan JS, Willams LM, Trayhurn P, Mercer JG: Leptin and leptin receptor mRNA and protein expression in the murine fetus and placenta. Proc Natl Acad Sci USA 1997;94: 11073–11078.

    Article  PubMed  CAS  Google Scholar 

  154. Masuzaki H, Ogawa Y, Sagawa N, et al.: Nonadipose tissue production of leptin: Leptinasna novel placenta-derived hormone in humans. Nat Med 1997;3:1029–1033.

    Article  PubMed  CAS  Google Scholar 

  155. Satoh N: The arcuate nucleus as a primary site of satiety effect of leptin in rats. Neurosci Lett 1997;224:149–152.

    Article  PubMed  CAS  Google Scholar 

  156. Chavez RA: Targeting of leptin to the regulated secretory pathway in pituitary AtP-20 cells. Curr Biol 1997;7:349–352.

    Article  PubMed  CAS  Google Scholar 

  157. Fei H: Anatomical localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues. Proc Natl Acad Sci USA 1997;94:7001–7005.

    Article  PubMed  CAS  Google Scholar 

  158. Bennett BD: A role for leptin and its cognate receptor in hematopoiesis. Curr Biol 1996;6: 1170–1180.

    Article  PubMed  CAS  Google Scholar 

  159. Chehab FF: Early onset of repro-ductive function in normal female mice treated with leptin. Science 1997;275:88–90.

    Article  PubMed  CAS  Google Scholar 

  160. Cioffi JA, Shafer AW, Zupancic TJ, et al.: Novel B 219/OB receptor soforms: Possible role of leptin in hematopoiesis and reproduction. Nature Medicine 1996;2:585–589.

    Article  PubMed  CAS  Google Scholar 

  161. Cioffi JA: The expression of leptin and its receptors in pre-ovulatory human follicles. Mol Human Reprod 1997;3:467–472.

    Article  CAS  Google Scholar 

  162. Gainsford T: Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc Natl Acad Sci USA 1996;93:14564–14568.

    Article  PubMed  CAS  Google Scholar 

  163. Serradeil-Le Gal C: Characterization and localization of leptin receptors in the rat kidneys. FEBS Lett 1997;404:185–191.

    Article  PubMed  CAS  Google Scholar 

  164. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P: Recombinant mouse OB protein: Evidence for a peripheral signal linkingadiposity and central neural networks. Science 1995;269:546–549.

    Article  PubMed  CAS  Google Scholar 

  165. Chua Jr. SC, Chung WK, Wu-Peng XS, et al.: Pheno types of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science 1996;271:994–996.

    Article  PubMed  CAS  Google Scholar 

  166. Clement K, Gamer C, Hager J, et al.: Indication for linkage of the human OB gene region with extreme obesity. Diabetes 1996; 45:687–690.

    Article  PubMed  CAS  Google Scholar 

  167. Halaas JL, Gajiwala KS, Maffei M, et al.: Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995;269: 543–546.

    Article  PubMed  CAS  Google Scholar 

  168. Halaas JL: Physiogical response to long-term peripheral and central leptin in fusion and obese mice. Proc Natl Acad Sci USA 1997; 94:8878–8883.

    Article  PubMed  CAS  Google Scholar 

  169. Harris RB: Recombinant leptin exchanges between parabiosed mice but does not reach equilibrium. Am J Physiol 1997;272: R1800-R1808.

    PubMed  CAS  Google Scholar 

  170. Harris RB: Loss of body fat in lean parabiotic partners of ob/ob mice. Am J Physiol 1997;272: R1809-R1815.

    PubMed  CAS  Google Scholar 

  171. Grunfeld C, Zhao C, Fullr J, Pollock A, Moser A, Feingold FJKR: Endotoxin and cytokines induce the expressionofleptin theob gene product, in hamsters. J Clin Inv 1996;97:2152–2157.

    CAS  Google Scholar 

  172. Sarraf P: Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. J. Exp Med 1997;185:171–175.

    Article  PubMed  CAS  Google Scholar 

  173. Ahima RS, Prabakaran D, Flier J: Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding. J Clin Invest 1998;101:1020–1027.

    PubMed  CAS  Google Scholar 

  174. Plata-Staman CR: Leptin (OB protein), neuropeptide Y, and interleukin-1 interactions as interface mechanisms for the regulation of feeding in health and disease. Nutrition 1996;12:718–719.

    Article  Google Scholar 

  175. Leal-Cemo A, Considine RV, Peino R, et al.: Serum immunoreactiveleptin levelsare increased in patients with Cushing's disease. Horm Metab Res 1996;28:711–713.

    Article  Google Scholar 

  176. Considine RV: Dexame thasone stimulates leptin release from human adipocytes: unexpected inhibition by insulin. J Cell Biochem 1997;65:254–258.

    Article  PubMed  CAS  Google Scholar 

  177. Miell JP: Dexamethasone induces an acute and sustained rise in circulating leptin levels in normal human subjects. Horm Metab Res 1996;28:704–707.

    PubMed  CAS  Google Scholar 

  178. Papaspyrou-Rao S: Dexamethasone increases leptin expression in humans in vivo. J. Clin Endocrinol Metab 1997;82:1632–1634.

    Article  Google Scholar 

  179. Evans R, Kamadar SJ, Duffy TM: Tumor-derived products induce IL-1a, IL-1b, TNF-α and IL-6 gene expression in murine macrophages: Distinctions between tumor-and bacterial endotoxin-induced gene expression. J Leuk Biol 1991;49:474–482.

    CAS  Google Scholar 

  180. Barton BE: The biological effects of interleuk in 6. Med Res Rev 1996;16:87–109.

    Article  PubMed  CAS  Google Scholar 

  181. Brouckaert P, Springgs DR, Demetri G, Kufe DW, Fiers W: Circulating interleukin 6 during continuous infusion of tumor necrosis factor and interferon γ. J Exp Med 1989;169:2257–2262.

    Article  PubMed  CAS  Google Scholar 

  182. Brown MA, Melcalf D, Gough NM: Leukaemia inhibitory factor and interleukin 6 are expressed at very low levels in the nomaladult mouse and are induced by inflamation. Cytokine 1994;6:300–309.

    Article  PubMed  CAS  Google Scholar 

  183. Naitoh Y, Fukata J, Tominaga T, Tamai S, Mori K, Imura H. Interleukin-6 stimulates the secretion of adrenocorticotropic hormone in conscious, freely-moving rats. Biochem Biophys Res Comm 1988;155:1459–1463.

    Article  PubMed  CAS  Google Scholar 

  184. Perlstein RS, Mougey EH, Jackson WE, Neta R: Interleukin-1 and interleukin-6 actsynergistically to stimulate the release of adrenocorticotropic hormone in vivo. Lymph Cyto Res 1991;10:141–146.

    CAS  Google Scholar 

  185. Salas MA, Evans SW, Levell MJ, Whicher JT: Interleukin-6 and ACTH act synergistically to stimulate the release of corticosterone from adrenal gland cells. Clinical and Experimental Immunology 1990;79:470–473.

    PubMed  CAS  Google Scholar 

  186. Woloski BMRNJ, Smith EM, Meyer WJ, Fuller GM, Blalock JE: Corticotropin-releasing factor activity of monokines. Science 1985;230:1035.

    Article  PubMed  CAS  Google Scholar 

  187. Barrachina MD, Martinez V, Wang L, Wei JY, Tache Y: Synergistic interaction between leptin and cholecystokinin to reduce shortterm food intake inleanmice. Proc Natl Acad Sci USA 1997;94: 10455–10460.

    Article  PubMed  CAS  Google Scholar 

  188. Levin N, Nelson C, Gurney A, Vandlen R, de Sauvage F: Decreased food intake does not completely account for adiposity reduction after ob protein infusion. Proc Natl Acad Sci USA 1996;93: 1726–1730.

    Article  PubMed  CAS  Google Scholar 

  189. Kamohara S, Burcellin, R, Halaas JL, Friedman JM, Charron MJ: Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 1997;389:374–377.

    Article  PubMed  CAS  Google Scholar 

  190. Barzilai N, Wang J, Massilon D, Vuguin P, Hawkins M, Rossetti L: Leptin selectively decreases visceral adiposity and enhances insulin action. J Clin Invest 1997;100:3105–3110.

    PubMed  CAS  Google Scholar 

  191. Simons JPFHA, Schols AMJW, Campfield LA, Wouters EFM, Saris WH: Plasma concentration of total leptin and human lungassociated cachexia. Clin Sci 1997;93:273–277.

    PubMed  CAS  Google Scholar 

  192. Muller G, Ertl J, Gerl M, Preibisch G: Leptin impairs metabolic actions of insulin in isolated rat adipocytes. J Biol Chem 1997;272: 10585–10593.

    Article  PubMed  CAS  Google Scholar 

  193. Alexanian R: 1991. Diagnosis and managemento-fmultiple myeloma. Seconded. In Neoplastic Diseases of the Blood, ed. P. H. Wiernick, 453–465. New York: Churchill Livingstone

    Google Scholar 

  194. Hilbert DM, Kopf M, Mock BA, Kohler G, Rudikoff S: Interleukin 6 is essential for in vivo development of B lineage neoplasms. J Exp Med 1995;182:243–248.

    Article  PubMed  CAS  Google Scholar 

  195. Klein B, Zhang X-G, Jourdan J, et al.: Interleukin-6 is the central tumor growth factor in vitro and in vivo in multiple myeloma. Eur Cytokine Net 1990;1: 193–201.

    CAS  Google Scholar 

  196. Zhang X-G, Klein B, Bataille R: Interleukin-6 is a potent myeloma-cell growth factor in patients with aggressive multiple myeloma. Blood 1989;74:11–13.

    PubMed  CAS  Google Scholar 

  197. Potter M, Boyce CR: Induction of plasma-cell neoplasms in strain BALB/c mice with mineral oil adjuvants. Nature 1962;193: 1086–1087.

    Article  PubMed  CAS  Google Scholar 

  198. Potter M: 1991. Experimental models of immunoglobulinsecreting tumors. Second ed. In Neoplastic Diseaseases of the Blood, ed. P. H. Wiernick, New York: Churchill Livingstone.

    Google Scholar 

  199. Feo-Zupparadi F, Taylor CW, Iwato K, et al.: Long-term engraftment of fresh human myeloma cells in SCID mice. Blood 1992;80: 2843–2850.

    Google Scholar 

  200. Huang Y-W, Richardson JA, Tong AW, Zhang B-Q, Stone MJ, Vitetta ES: Disseminated growth of a human multiple myeloma cell line in mice with severe combined immunodeficiency disease. Can Res 1993;53:1392–1396.

    CAS  Google Scholar 

  201. Suzuki H, Yasukawa K, Saito T: et al.: Anti-human interleukin-6 receptor antibody inhibits human myeloma growth in vivo. Eur J Immunol 1992;22:1989–1993.

    Article  PubMed  CAS  Google Scholar 

  202. Alsina M, Boyce BF, Mundy GR, Roodman GD: An in vivo model of human multiple myeloma bone disease. Stem Cells 1995;13:48–50.

    PubMed  Google Scholar 

  203. Hardin J, Macleod S, Grigorievan I, Chang R, Xiao H, Epstein J: Interleukin-6 prevents dexamethasone-induced myeloma cell death. Blood 1994;84:3063–3070.

    PubMed  CAS  Google Scholar 

  204. Taga T, Hibi M, Murakami M, et al.: Interleukin-6 Receptors and Signals. Interle ukins: Molecular Biology and Immunology, ed. T. Kishimoto, 1992, 51, Basel: Kargel.

    Google Scholar 

  205. Kawano M, Hirano T, Matsuda T, et al.: Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature 1988;332:83–84.

    Article  PubMed  CAS  Google Scholar 

  206. Hata H, Xiao H, Petrucci MT, Woodliff J, Chang R, Epstein J: Interleukin-6 gene expression in multiple myeloma: A characteristic of immature tumor cells. Blood 1993;81:3357–3364.

    PubMed  CAS  Google Scholar 

  207. Kawano M, Tanaka H, Ishikawa H, et al.: Interleukin-1 accelerates growth of myeloma cells through interleukin-6 in human myeloma. Blood 1989;73:2145–2148.

    PubMed  CAS  Google Scholar 

  208. Ludwig H, Nachbaur DM, Fritz E, Krainer M, Huber H: Interleukin-6 is a prognostic factor in multiple myeloma. Blood 1991;77:2794–2795.

    PubMed  CAS  Google Scholar 

  209. Bataille R, Jourdan M, Zhang X-G, Kein B: Serum levels of interleukin 6, a potent myeloma cell growth factor, as a reflection of disease severity in plasma cell dyscrasias. J Clin Invest 1989;84: 2008–2011.

    Article  PubMed  CAS  Google Scholar 

  210. Harrison LE: 1996. Animal models of cancer cachexia. In Protein and Amino Acid Metabolism in Cancer Cachexia, eds. G.W.T. Pisters, M.F. Brennan, 1–19, New York: Chapman & Hall.

    Google Scholar 

  211. Berman RS: 1996. Non-invasive techniques to evaluate protein and amino acid metabolism. In Protein and Amino Acid Metabolism in Cancer Cachexia, eds P.W.T. Pisters, M.F. Brennan, 21–31. New York: Chapman & Hall.

    Google Scholar 

  212. Abumrad N, Ystueta SM, Molina P, Bursztein S: 1996 Ertergy Metabolism. Second ed. In Nutrition and Metabolism in the Surgical Patient, ed. J.E. Fischer, 105–127, New York, Little Brown & Co.

    Google Scholar 

  213. Tabibzadeh SS, Poubouris D, May LT, Sehgal PB: Immunoreactivity in human tumors. Am J Pathol 1989;135:427–433.

    PubMed  CAS  Google Scholar 

  214. Sherry BA, Gelin J, Fong Y, et al.: Anticachectin/tumor necrosis factor-a antibodies attenuate development of cachexia in tumor models. FASEB J 1989;3: 1956–1962.

    PubMed  CAS  Google Scholar 

  215. Soukas A, Cohen P, Socci ND, Friedman JM: Leptin-specific pattems of gene expression in white adipose tissue. Gen Develop 2000;14:963–980.

    CAS  Google Scholar 

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  1. Beverly E. Barton Ph.D.

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    Barton, B.E. IL-6-like cytokines and cancer cachexia. Immunol Res 23, 41–58 (2001). https://doi.org/10.1385/IR:23:1:41

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