Abstract
Determination of plasma and tissue cytokinelevels in inflammatory bowel disease have frequentlyresulted in conflicting data. In the present study wedetermined in patients with ulcerative colitis (UC), the levels of the proinflammatory cytokinesinterleukin (IL)-1β, IL-6, interferon(IFN)-γ, and tumor-necrosis factor (TNF)-αliberated by peripheral blood mononuclear cells (PBMC)and lamina propria mononuclear cells (LPMC) after 48-hrculture with pokeweed mitogen (PWM). IL-1β, IL-6,IFN-γ and TNF-α in the supernatant weredetected by ELISA. Results show low basal levels ofIL-1β secretion by PBMC and LPMC, and a considerableincrease after mitogen stimulation. Basal IL-6production by PBMC was higher in UC patients than incontrols [2029 pg/ml, CI9 (–165 to4223) vs 572 pg/ml (–383 to 1527) respectively, P = 0.05] and also afterPWM activation [14,995 pg/ml (7759 -22230) vs 6598 pg/ml(3240-9956), respectively, P = 0.05]. In LPMC, nodifferences in IL-6 secretion were observed. TNF-α in activated PBMC of patients with UC was notsignificantly increased in relation to control (P =0.09). No constitutive secretion of IFN-γ wasobserved in mononuclear cells. IFN-γ levelssecreted by activated LPMC were lower in patients withUC than in controls [1571 pg/ml (–108 to 3251) vs7953 pg/ml (3851-12,055), respectively, P = 0.03]. Theseresults suggest that IL-6, IL-1β, and TNF-α participate as mediators in the inflammatoryphenomena observed in UC. Further studies are necessaryto evaluate the role of IFN-γ in thiscondition.
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REFERENCES
Sartor B: Cytokines in intestinal inflammation: Pathophysiological and clinical considerations. Gastroenterology 106:533-539, 1994
Braegger CP, MacDonald TT: Immune mechanisms in chronic inflammatory bowel disease. Ann Allergy 72:135-141, 1994
Radford-Smith G, Jewell DP: Cytokines and inflammatory bowel disease. Baillieres Clin Gastroenterol 10:151-164, 1996
Jongen-Laverencic M, Peeters HRM, Rozemuller H, Rombouts WJC, Martens ACM, Vreugdenhil G, Pillay M, Cox PH, Bijser M: IL-6-induced anemia in rats: Possible pathogenesis implications for anemia observed in chronic inflammation. Clin Exp Immunol 103:328-334, 1996
Sun XM, Hsueh W: Bowel necrosis induced by tumor necrosis factor in rats mediated by platelet activating factor. J Clin Invest 81:1328-1335, 1988
Theodorou V, Eutamene H, Fioramonti J, Junien JL, Bueno L: Interleukin 1 induces a neurally mediated colonic secretion in rats: Involvement of mast cells and prostaglandins. Gastroenterology 106:1493-1500, 1994
McKay DM, Croitoru K, Perdue M: T cell-monocyte interactions regulate epithelial physiology in a co-culture mode l of inflammation. Am J Physiol 270:C418-C428, 1996
Heyman M, Darmon N, Dupont C, Dugas B, Hirribaren A, Blaton A, Desjeux JF: Mononuclear cells from infants allergic to cow's milk secrete tumour necrosis factor a, altering intestinal function. Gastroenterology 106:1514-1523, 1994
Rodriguez P, Heyman M, Candahl C, Blaton MA, Bouchaud C: Tumour necrosis factor-α induces morphological and functional alterations of intestinal HT29cl.19A cell monolayer. Cytokine 7:441-448, 1995
Sütas Y, Autio S, Rantala I, Isolauri E: IFN-γ enhance s macromolecular transport across Peyer's patches in suckling rats: Implications for natural immune responses to dietary antigens early in life. J Pediatr Gastroenterol Nutr 24:162-169, 1997
Madara JL, Stafford J: Interferon-γ affects barrier function of cultured intestinal epithelial monolayers. J Clin Invest 83:724-727, 1989
Colgan SP, Parkos CA, Delp C, Arnaout MA, Madara JL: Neutrophil migration across cultured intestinal epithelial monolayers is modulated by epithelial exposure to IFN-γ in a highly polarized fashion. J Cell Biol 00:785-798, 1993
Ouyang Q, El-Youssef M, Yenn-Lieberman B, Sapatnekar W, Youngman KR, Kusugami K, Fiocchi C: Expression of HLA-DR antigens in inflammatory bowel disease mucosa: Role of intestinal lamina propria mononuclear cell-derived interferon gamma. Dig Dis Sci 33:1528-1537, 1988
Krajci P, Taskene K, Kvale D, Brandtzaeg P: Interferongamma stimulation of messenger RNA for human secretory component (poly-Ig receptor) depends on continuous intermediate synthesis. Scand J Immunol 37:251-256, 1993
Van Dullemen HM, Van Deventer SJH, Hommes DW, Bijl HA, Jansen J, Tytgat GN, Woody J: Treatment of Crohn's disease with anti-tumour necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology 109:129-135, 1995
Reinecker HC, Steffen M, Witthoeft T, Pfuelger Y, Schreiber S, MacDermott RP, Raedler A: Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1β by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease. Clin Exp Immunol 94:174-181, 1993
Toyoda H, Wang SJ, Yang HY, Redford A, Magalong D, Tyan D, McElree CK, Pressman SR, Shanahan F, Targan SR, Rotter JI: Distinct associations of HLA class II genes with inflammatory bowel disease. Gastroenterology 104:741-748, 1993
Walmsley RS, Ibbotson JP, Chahal H, Allan RN: Antibodies to Mycobacterium paratuberculosis in Crohn' s disease. QJM 89:217-221, 1996
Braegger C: Immunopathogenesis of chronic inflammatory bowel disease. Acta Paediatr Suppl 395:18-21, 1994
Greenwald BD, James SP: Immunology of inflammatory bowel disease. Curr Opin Gastroenterol 13:293-301, 1997
Bookman MA, Bull DM: Characteristics of isolated intestinal mucosal lymphoid cells in inflammatory bowel disease. Gastroenterology 77:503-510, 1979
Kusugami K, Haruta J, Ieda M, Shinoda M, Ando T, Kuroiwa A, Ina K, Iokawa H, Ishihara A, Sarai S, Saito Y, Tanimoto M, Morise K: Phenotypic and functional characterization of T-cell lines generated from colonoscopic biopsy specimens in patients with ulcerative colitis. Dig Dis Sci 40:198-210, 1995
Cole AT, Pilkington BJ, McLaughlan J, Smith C, Balsitis M, Hawkey CJ: Mucosal factors inducing neutrophil movement in ulcerative colitis: The role of interleukin-8 and leukotrien B4. Gut 39:705-710, 1996
Olson AD, Ayass M, Chensue S: Tumor necrosis factor and IL1-β expression in pediatric patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 16:241-246, 1993
MacDonald TT, Hutchings P, Coy MY, Murch S, Cooke A: Tumour necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflammed human intestine. Clin Exp Immunol 81:301-305, 1990
Isaacs KL, Sartor B, Haskill S: Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification. Gastroenterology 103:1587-1595, 1992
Mahida YR, Kurlak L, Gallagher A, Hawkey CJ: High circulating concentrations of interleukin 6 in active Crohn's disease but not ulcerative colitis. Gut 32:1531-1534, 1991
Murata Y: Alterations of immunoglobulin secretion, interleukin 2 (IL-2) and IL-6 production by peripheral blood mononuclear cells from patients with ulcerative colitis. In Procee dings of the Sixth International Congress of Immunology. M Tsuchiya, H Nagura, T Hibi, I Moro, (eds). Frontiers of Mucosal Immunology. Amsterdam, Elsevier 1990, pp 719-722
Jones SC, Crabtree JE, Rembacken BJ, Dixon ME, Trejdosiewicz: Mucosal interleukin-6 secretion in ulcerative colitis. Effects of anti-inflammatory drugs and T-cell stimulation. Scand J Gastroenterol 29:722-728, 1994
Lieberman BY, Fiocchi C, Youngman KR, Sapatnekar WK, Proffit MR: Interferon γ production by human intestinal mucosal mononuclear cells. Decreased levels in inflammatory bowel disease. Dig Dis Sci 33:1297-1304, 1988
Breese E, Braegger CP, Corrigan CJ, Walker-Smith JA, Mac-Donald TT: Interleukin-2 and interferon-γ-secreting T cells in normal and diseased human intestinal mucosa. Immunology 78:127-131, 1993
Kusugami K, Youngman KR, West GA, Fiocchi C: Intestinal immune reactivity to interleukin 2 differs among Crohn's disease, ulcerative colitis, and controls. Gastroenterology 97:1-8, 1989
Fuss IJ, Neurath M, Boirivant M, Klein JS, de la Motte C, Strong SA, Fiocchi C, Strober W: Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn' s disease LP cells manifest increased secretion of IFN-gamma, where as ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol 157:1261-1270, 1996
Mossmann TR, Coffman RL: Th1 and Th2 cells: Different pattern of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145-174, 1989
De Waal M, Abrams J, Bennet B, Figdor CG, de Vries JE: Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: An autoregulatory role of IL-10 produced by monocytes. J Exp Med 174:1209-1220, 1991
Niessner M, Volk BA: Altered Th1/Th2 cytokine profile in the intestinal mucosa of patients with inflammatory bowel diseaseas assessed by quantitative reversed transcribed polymerase chain reaction (RT-PCR). Clin Exp Immunol 101:428-435, 1995
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Gotteland, M., Lopez, M., Munoz, C. et al. Local and Systemic Liberation of Proinflammatory Cytokines in Ulcerative Colitis. Dig Dis Sci 44, 830–835 (1999). https://doi.org/10.1023/A:1026690631693
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DOI: https://doi.org/10.1023/A:1026690631693