CYTOKINE MESSENGER-RNA EXPRESSION AND PROLIFERATION STATUS OF INTESTINAL MONONUCLEAR-CELLS IN NONINFLAMED GUT AND CROHNS-DISEASE

T-cell activation and local cytokine production probably contribute to the pathogenesis of Crohn's disease. This study investigates the prol iferative status of intestinal mononuclear cells (MNC) and cytokine me ssenger RNA (mRNA) production in gut tissue sections from patients wit h Crohn's disease and noninflamed controls. mRNA in situ hybridization was performed using P-33-labelled riboprobes for human interleukin (I L)-1 beta, IL-2, IL-4, IL-5, IL-6, tumour necrosis factor-alpha and in terferon-gamma. The expression of the proliferation-associated antigen Ki-67 was analysed by immunohistochemical single and double staining. Compared with controls, where proliferation of MNC and cytokine expre ssion was restricted to mucosal lymphoid follicles, inflamed gut tissu e contained increased numbers of cells express ing cytokine mRNA, most prominently IL-1 beta and IL-6, but also interferon-gamma and tumour necrosis factor-alpha. Proliferating T-cells were increased in number, and small amounts of IL-2-expressing cells were detected. IL-4 was ex pressed by a few cells exclusively in follicular germinal centres. IL- 5 was negative. Proinflammatory cytokines are strongly expressed in si tu in Crohn's disease and largely predominate over lymphokine mRNA. Ou r results provide in situ evidence of a local lymphocyte response in C rohn's disease with characteristics of a delayed-type hypersensitivity reaction.