Interleukin (IL)-13 and IL-4 Are Potent Inhibitors of IL-8 Secretion by Human Intestinal Epithelial Cells

Intestinal epithelial cells are able to producesoluble mediators that initiate or amplify inflammatoryevents in the intestinal mucosa. Interleukin (IL)-8 issuggested to be a cytokine playing a major role during the acute and chronic processes ininflammatory bowel disease (IBD). TH-2 cytokines havebeen described as down-regulating the inflammatoryresponse. We analyzed the effects of IL-10, IL-13, and IL-4 on IL-8 secretion in intestinalepithelial cells. The human colonic epithelial cell lineCaco-2 and freshly isolated intestinal epithelial cellswere used. Cells weRestimulated with IL-1beta after treatment with TH-2 cytokines. Levels of IL-8were determined by employing enzyme-linked immunosorbentassay (ELISA). Stimulation with IL-1beta results in atime-dependent IL-8 secretion. The addition of IL-4 and IL-13, but not IL-10, to activatedepithelial cells resulted in a strong decrease in IL-8secretion. Maximal inhibition required that TH-2cytokines be added up to 60 min before or simultaneous with stimulatory agents. We present novelfindings that IL-4 and IL-13 strongly down-regulate IL-8secretion from intestinal epithelial cells. Amicroenvironment containing high concentrations of IL-4and IL-13 may alter The recruitment of immune cellsto enterocytes at least partly by inhibiting IL-8production. This inhibition might diminish the severityof the intestinal inflammatory response and, thus reduce clinical disease activity.