CYTOKINES INCREASE PROLIFERATION OF HUMAN INTESTINAL SMOOTH-MUSCLE CELLS - POSSIBLE ROLE IN INFLAMMATION-INDUCED STRICTURE FORMATION

Crohn's disease is an idiopathic, chronic inflammation of the gastrointestinal tract that causes narrowing and stricturing of primarily the small and large intestine. Although the mechanism(s) by which chronic inflammation promotes stricture formation remain to be defined, it does appear to be associated histologically with a hyperplasia of smooth muscle cells and an increased deposition of collagen within the bowel wall. The objective of this study was to assess the effect of two proinflammatory cytokines, tumor necrosis factor and interleukin-1, on the proliferation of human intestinal smooth muscle cells in vitro. Human intestinal smooth muscle cells were seeded at subconfluent densities into 24-well plates in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. Human recombinant tumor necrosis factor (0.1-100 ng/ml), interleukin-1 (0.1-500 ng/ml), or control medium (without cytokines) was then added to the cells and incubation continued for 48 or 72 h. Proliferation was determined by the incorporation of tritiated thymidine, added during the final 18 h, into the cellular DNA of the smooth muscle cells. Both cytokines caused a significant dose-dependent increase in intestinal smooth muscle cell proliferation relative to control. These results suggest that the interleukin-1 and tumor necrosis factor produced during chronic inflammation in vivo may enhance the proliferation of smooth muscle cells within the intestinal bowel wall and hence potentially contribute to the narrowing and stricturing of the intestine that is observed in Crohn's disease.