Abstract
Patterns of cytokine profiles have emerged for different forms of inflammatory bowel disease with a predominance of type 1 cytokines in patients with Crohn disease and type 2 cytokine expression in patients with ulcerative colitis. Most of these studies have involved older patients with long-standing disease or after various therapeutic interventions, and patterns of cytokine expression were hypothesized to be influenced by these factors. To evaluate for these possibilities, we studied 23 patients (15 boys) with newly diagnosed Crohn disease (n = 14) or ulcerative colitis. Their mean age at diagnosis was 13.1 ± 2.9 y (mean ± SD). Healthy control subjects (n = 9) were previously obtained. Peripheral blood intracellular cytokine analysis was performed within 24 h using a modification of Becton Dickinson's FastImmune Cytokine system. Multiparametric flow cytometry and phenotyping of lymphocytes was performed. T-cell populations were defined as type 1 being CD69+, CD3+, and interferon-γ+ and type 2 being CD69+, CD3+, and IL-4+. The median percent of type 1 T cells from normal subjects (2.8%) was similar to that of ulcerative colitis subjects (1.8%, p > 0.20) but greater than that of Crohn disease subjects (0.55%, p = 0.05). The median percent of type 2 lymphocytes in normal subjects (1.8%) was greater than that of ulcerative colitis subjects (0.35%, p = 0.02) but was similar to that of Crohn disease subjects (1.1%, p > 0.20). Serial determinations showed the median percent of type 2 T cells increased in ulcerative colitis patients as remission was induced. Reduced activated peripheral type 1 T cells of newly diagnosed, untreated children are similar to interferon-γ expression in mucosa of adults with postoperative recurrence. Reduced type 2 cytokine expression patterns in subjects with ulcerative colitis are similar to lamina propria T-cell expression levels in adults and improve with disease remission.
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Abbreviations
- CD:
-
Crohn disease
- UC:
-
ulcerative colitis
- Th:
-
T helper
- IFN-γ:
-
interferon-γ
- IBD:
-
inflammatory bowel disease
- PCDAI:
-
pediatric Crohn disease activity index
- FACS:
-
fluorescence-activated cell sorter
References
Abbas AK, Murphy KM, Sher A 1996 Functional diversity of helper T lymphocytes. Nature 383: 787–793
Romaganni S 1999 Th1/Th2 cells. Inflamm Bowel Dis 5: 285–294
Fiocchi C 1998 Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 115: 182–205
Mullin GE, Maycon ZR, Braun-Elwert L, Cerchia R, James SP, Katz S, Weissman GS, McKinley MJ, Fisher SE 1996 Inflammatory bowel disease mucosal biopsies have specialized lymphokine mRNA profiles. Inflamm Bowel Dis 2: 16–26
Camoglio L, Te Velde AA, Tigges AJ, Das PK, Van Deventer SJH 1998 Altered expression of interferon-γ and interleukin-4 in inflammatory bowel disease. Inflamm Bowel Dis 4: 285–290
Fuss IJ, Neurath M, Boirivant M, Klein JS, de la Motte C, Strong SA, Fiocchi C, Strober W 1996 Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. J Immunol 157: 1261–1270
West GA, Matsuura T, Levine AD, Klein JS, Fiocchi C 1996 Interleukin 4 in inflammatory bowel disease and mucosal immune reactivity. Gastroenterology 110: 1683–1695
Inoue S, Matsumoto T, Iida M, Mizuno M, Kuroki F, Hoshika K, Shimizu M 1999 Characterization of cytokine expression in the rectal mucosa of ulcerative colitis: correlation with disease activity. Am J Gastroenterol 94: 2441–2446
Desreumaux P, Brandt E, Gambiez L, Emilie D, Geboes K, Klein O, Ectors N, Cortot A, Capron M, Colombel JF 1997 Distinct cytokine patterns in early and chronic ileal lesions of Crohn's disease. Gastroenterology 113: 118–126
Lilic D, Cant AJ, Abinun M, Calvert JE, Spickett GP 1997 Cytokine production differs in children and adults. Pediatr Res 42: 237–240
Hyams J, Davis P, Lerer T, Colletti RB, Bousvaros A, Leichtner A, Benkov K, Justinich C, Markowitz J 1997 Clinical outcome of ulcerative proctitis in children. J Pediatr Gastroenterol Nutr 25: 149–152
Hyams JS, Ferry GD, Mandel FS, Gryboski JD, Kibort PM, Kirschner BS, Griffiths AM, Katz AJ, Grand RJ, Boyle JT, Michener WM, Levy JS, Lesser ML 1991 Development and validation of a pediatric Crohn's disease activity index. J Pediatr Gastroenterol Nutr 12: 439–447
Hyams JS, Mandel F, Ferry GD, Gryboski JD, Kibort PM, Kirschner BS, Griffiths AM, Katz AJ, Boyle JT 1992 Relationship of common laboratory parameters to the activity of Crohn's disease in children. J Pediatr Gastroenterol Nutr 14: 216–222
Ferry B, Antrobus P, Huzicka I, Farrell A, Lane A, Chapel H 1997 Intracellular cytokine expression in whole blood preparations from normals and patients with atopic dermatitis. Clin Exp Immunol 110: 410–417
Jung T, Schauer U, Heusser C, Neumann C, Rieger C 1993 Detection of intracellular cytokines by flow cytometry. J Immunol Methods 159: 197–207
Vikingsson A, Pederson K, Muller D 1994 Enumeration of IFN-gamma producing lymphocytes by flow cytometry and correlation with quantitative measurement of IFN-gamma. J Immunol Methods 173: 219–228
Fiocchi C, Fukushima K, Strong SA, Ina K 1996 Pitfalls in cytokine analysis in inflammatory bowel disease. Aliment Pharmacol Ther 10( suppl 2): 63–69
Sands BE, Tremaine WJ, Sandborn WJ, Rutgeerts PJ, Hanauer SB, Mayer L, Targan SR, Podolsky DK 2001 Infliximab in the treatment of severe, steroid-refractory ulcerative colitis. Inflamm Bowel Dis 7: 83–88
Rutgeerts P, D'Haens G, Targan S, Vasiliaukas E, Hanauer SB, Present DH, Mayer L, Van Hogezand RA, Braakman T, DeWoody KL, Schaible TF, Van Deventer SJH 1999 Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease. Gastroenterology 117: 761–769
Brynskov J, Freund L, Rasmussen SN, Lauritsen K, Schaffalitzky de Muckadell O, Williams N, MacDonald AS, Tanton R, Molina F, Campianini MC, Bianchi P, Ranzi T, Quarto di Palo F, Malchow-Moller A, Thomsen OO, Tage-Jensen U, Binder V, Riis P 1989 A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease. N Engl J Med 321: 845–850
Feagan BG, McDonald JWD, Rochon J, Laupacis A, Fedorak RN, Kinnear D, Saibil F, Groll A, Archambault A, Gillies R, Valberg B, Irvine EJ 1994 Low-dose cyclosporine for the treatment of Crohn's disease. N Engl J Med 330: 1846–1851
Bouhnik Y, Lemann M, Mary JY, Scemama G, Tai R, Matuchansky C, Modigliani R, Rambaud C 1996 Long-term follow-up of patients with Crohn's disease treated with azathioprine or 6-mercaptopurine. Lancet 347: 215–219
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Supported by a grant from John A Weibe, Jr. Healthcare Research and Education Fund.
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Mack, D., Beedle, S., Warren, J. et al. Peripheral Blood Intracellular Cytokine Analysis in Children Newly Diagnosed with Inflammatory Bowel Disease. Pediatr Res 51, 328–332 (2002). https://doi.org/10.1203/00006450-200203000-00011
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DOI: https://doi.org/10.1203/00006450-200203000-00011
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