IL-4, IL-10 AND IL-13 DOWN-REGULATE MONOCYTE-CHEMOATTRACTING PROTEIN-1 (MCP-1) PRODUCTION IN ACTIVATED INTESTINAL EPITHELIAL-CELLS

Several studies have demonstrated that intestinal epithelial cells pla y a major role in the initiation and perpetuation of intestinal inflam mation by secreting proinflammatory cytokines and chemokines. MCP-1 is suggested to be a chemokine that plays a major part during intestinal inflammation in inflammatory bowel disease (IBD). Immunoregulatory cy tokines such as IL-4, IL-10 and IL-13 have been described to exert ant i-inflammatory properties on various cell types. The aim of our study was to determine the effect of Th2 cytokines on the production of MCP- I by activated intestinal epithelial cells. We examined Caco-2 cells a s well as intestinal epithelial cells which were isolated from surgica l specimens. Production of the chemokine MCP-1 was determined under st imulated and non-stimulated conditions. IL-4, IL-10 and n-13 were adde d to stimulated epithelial cells under various culture conditions. Sup ernatants were analysed for cytokine concentrations using ELISAs. Unde r stimulation with physiological agents like IL-1 beta or tumour necro sis factor-alpha (TNF-alpha), we observed markedly increased concentra tions of MCP-I in supernatants of Caco-2 cells and intestinal epitheli al cells. lL-4, IL-10 and IL-13 all had the capacity to down-regulate the production of MCP-1 in Caco-2 cells as well as in freshly isolated epithelial cells. Caco-2 cells which were primed with Th2 cytokines 2 4 h before stimulation were subsequently decreased in their ability to be stimulated by IL-1 beta or TNF-alpha for MCP-1 production. As MCP- 1 has been shown to play a major role during intestinal inflammation, the in vitro suppression of MCP-1 in enterocytes suggests the in vivo use of regulatory cytokines in patients with active IBD.