Abstract
Active ulcerative colitis (UC) is associated with elevated granulocytes and monocytes/macrophages (GM) which show activation behavior and increased survival time. Further, fecal calprotectin (a stable neutrophil protein) level parallels intestinal inflammation and can predict UC relapse. Since GM are major sources of inflammatory cytokines and chemokines, they are suspected to have roles in the initiation and perpetuation of UC. Our objective was to investigated relationships between peripheral blood (PB) neutrophils, calprotectin, and UC disease activity. Full PB and calprotectin were determined in 69 healthy controls and 31 patients with UC, then 7 randomly selected patients received GM adsorptive apheresis (GMA) with Adacolumn, 10 sessions of 60-min duration each. Patients with UC had higher neutrophil counts (P<0.001), but lower lymphocyte counts (P<0.001) compared with controls. Further, fecal calprotectin levels showed a correlation with UC clinical activity index (CAI; P<0.001) and mucosal inflammation (P<0.001). Following GMA, there were falls in neutrophils (P<0.02), CAI (P<0.02) and calprotectin (P<0.02). In conclusion, GM appear to contribute to intestinal inflammation and UC activity and reduction of these cells by GMA should benefit patients with active UC. Further, the correlations among calprotectin, UC activities, and PB neutrophils should serve as the basis for preemptive actions to control this disease.
Similar content being viewed by others
REFERENCES
McCarthy DA, Rampton DS, Liu Y-C: Peripheral blood neutrophils in inflammatory bowel disease. Morphological evidence of in vivo activation in active disease. Clin Exp Immunol 86:489–493, 1991
Grisham MB, Yamada T: Neutrophils, nitrogen oxides and inflammatory bowel disease, neuro-immuno-physiology of the gastroint-ertinal mucosa. Ann NY Acad Sci 664:103–115, 1992
Allison MC, Dhillon AP, Lewis WG, Pounder RE (eds): Inflammatory Bowel Disease. London, Mosby, 1998, pp 15–95
Tibble JA, Sigthorsson G, Bridger D, Fagerhol MK, Bjarnason I: Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 119:15–22, 2000
Bjarnason I, Macpherson A, Menzies IS: Intestinal permeability: The basics. In Inflammatory Bowel Disease. Basic Research, Clinical Implications and Trends in Therapy. LR Sutherland, SM Collins, F Martin, RS McLeod, SR Targan, JL Wallace, CN Williams (eds). Dordrech, Kluwer Academic Press, 1994, pp 53–70
Bjarnason I, Macpherson A, Hollander D: Intestinal permeability: An overview. Gastroenterology 108:1566–1581, 1995
Cassatella MA: The production of cytokines by polymorphonuclear neutrophils. Immunol Today 16:21–26, 1995
Nikolaus S, Bauditz J, Gionchetti P: Increased secretion of pro-inflammatory cytokines by circulating polymorphonuclear neutrophils and regulation by interleukin-10 during intestinal inflammation. Gut 42:470–476, 1998
Hanai H, Watanabe F, Takeuchi K, Saniabadi A, Bjarnason I: Leucocyte adsorptive apheresis for the treatment of active ulcerative colitis: a prospective uncontrolled pilot study. Clin Gastroenterol Hepatol 1:28–35, 2003
Brannigan AE, O'Connell PR, Hurley H: Neutrophil apoptosis is delayed in patients with inflammatory bowel disease. Shock 13:361–366, 2000
Roseth AG, Schmidt PN, Fagerhol MK: Correlation between faecal excretion of Indium-111-labelled granulocytes and calprotectin, a granulocyte marker. Scand J Gastroenterol 34:50–54, 1999
Lee, A, Whyte M, Haslett C: Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators. J Leukoc Biol 54:283–288, 1993
Meagher LC, Cousin JM, Seckl JR, Haslett C: Opposing effects of glucocorticoids on the rate of appoptosis in neutrophilic and eosinophilic granulocytes. J Immunol 156:4422–4428, 1996
Limburg P, David M, Ahlquist A, Sandborn WJ: Faecal calprotectin levels predict colorectal inflammation among patients with chronic diarrhoea referred for colonoscopy. Am J Gastroenterol 95:2831–287, 2000
Matts SGF: The value of rectal biopsy in the diagnosis of ulcerative colitis. Q J Med New Ser XXX 120:393–407, 1961
Rachmilewitz D (on behalf of an international study group): Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: A randomized trial. Br Med J 298:82–86, 1989
Saniabadi AR, Hanai H, Takeuchi K, Bjarnason I, Lofberg R: Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial 7:48–59, 2003
Hiraishi K, Takeda Y, Shiobara N, Shibusawa H, Jimma F, Kashiwagi N, Saniabadi AR, Adachi M: Studies on the mechanisms of leukocyte adhesion to cellulose acetate beads: An in vitro model to assess the efficacy of cellulose acetate carrier-based granulocyte and monocyte adsorptive apheresis. Therap Apher Dial 7:334–340, 2003
D'Arrigo C, Candal-Couto JJ, Greer M, Veale DJ, Woof JM: Human neutrophil Fc receptor-mediated adhesion under flow: a hallow fiber model of intravascular arrest. Clin Exp Immunol 100:173–179, 1993
Springer TA: Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol 57:827–872, 1995
Sharon P, Stenson WF: Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease. Gastroentrology 86:453–460, 1984
Sawada K: Leukocytapheresis as an adjunct to conventional medication for inflammatory bowel disease. Dis Colon Rectum 46 (Suppl 10): S66–S77, 2003
Hanai H, Watanabe F, Saniabadi A, Matsushita I, Takeuchi K, Iida T: Therapeutic efficacy of granulocyte and monocyte adsorption apheresis in severe active ulcerative colitis. Dig Dis Sci 47: 2349–2353, 2002
Premchand P, Takeuchi K, Bjarnason I: Selective bloodletting for severe ulcerative colitis. Scand J Gastroenterol 2004 (in press)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hanai, H., Takeuchi, K., Iida, T. et al. Relationship Between Fecal Calprotectin, Intestinal Inflammation, and Peripheral Blood Neutrophils in Patients with Active Ulcerative Colitis. Dig Dis Sci 49, 1438–1443 (2004). https://doi.org/10.1023/B:DDAS.0000042243.47279.87
Issue Date:
DOI: https://doi.org/10.1023/B:DDAS.0000042243.47279.87