Type 1 T-helper cell predominance in granulomas of Crohn's disease

OBJECTIVE: The pathogenesis of Crohn's disease (CD) is thought to be associated with production of several cytokines, especially type-1 cytokines. To elucidate the in sial cytokine profiles in CD, cytokine-containing cells were localized by immunohistochemistry, with special attention to noncaseating granulomas. The results were compared with those from studies of ulcerative colitis (UC). METHODS: We adopted the biotin-streptavidin-peroxidase method on frozen sections obtained at surgery from patients with CD or UC, and we immunohistochemically examined the expression of several cytokines (interferon-gamma, interleukin-2, -4, -10, and -12). RESULTS: In normal colonic tissue, expression of these cytokines was rare except for interleukin-4. In actively inflamed areas of CD, increased expression of all cytokines by mononuclear cells was observed. In contrast, granulomas in CD involved interferon-gamma(+) lymphocytes and interleukin-12(+) macrophage-lineage cells (epithelioid cells and multinucleated giant cells) but few interleukin-4(+) or -10(+) cells. Actively inflamed areas of UC also showed an increase in the number of cytokine-containing cells; however, quantitative analysis revealed that there was more expression of interferon-gamma and interleukin-12, and less of interleukin-10, in CD than in UC, indicating the presence of more type 1 T-helper cells in CD tissue than in UC. CONCLUSIONS: The findings of the present study suggest that granulomas of CD are coupled with type 1 T-helper responses; these responses may contribute to the pathogenesis of this disease. (Am J Gastroenterol 1999;94: 2149-2155. (C) 1999 by Am. Coll. of Gastroenterology).