CYTOKINE EXPRESSION IN INTESTINAL MUCOSAL BIOPSIES - IN-SITU HYBRIDIZATION OF THE MESSENGER-RNA FOR INTERLEUKIN-1-BETA, INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR-ALPHA IN INFLAMMATORY BOWEL-DISEASE

Etiology and pathogenesis of inflammatory bowel disease (IBD) remain o bscure. There is substantial evidence that proinflammatory cytokines s uch as Interleukin-1 beta (IL-1 beta), Interleukin-6 (IL-6) and Tumour Necrosis Factor-alpha (TNF-alpha) exhibit a key role in tile the infl ammatory process, In situ hybridisation can depict individual cells pr oducing cytokine mRNA. We performed hybridisation with antisense probe s specific for IL-1 beta, IL-6 and TNF-alpha on sections of paraffine- embedded biopsies. Specimens obtained from three control persons and s ix cases of Crohn's disease (CD) were investigated. Only few positive cells were found in tissue sections of control persons, clusters of la mina propria cells or epithelial cells containing cytokine mRNA were n ot observed. Inflammatory bowel disease tissue contained large numbers of cells producing mRNA specific for the three proinflammatory cytoki nes assayed. IL-1 beta, IL-6 and TNF-alpha mRNA were predominantly det ected corresponding to cells of the lamina propria. Single cells conta ining mRNA specific for IL-6 were also found among the epithelial lini ng of intestinal crypts. Epithelial cells containing IL-1 beta and IL- 6 mRNA were found in specimens derived from one patient with Crohn's d isease. Notably, large amounts of cells containing cytokine mRNA were not only found in inflamed, but also in macroscopically normal mucosa. In conclusion, using proinflammatory cytokines as a model, we establi shed in situ hybridisation on sections of mucosal biopsies permitting further insight into immune activation at individual cell level.