Cytokine interactions with epithelium

Abstract

Cytokines are a family of proteins that serve as intracellular messengers within the immune system, and as growth factors for several cell types. Recent studies indicate that intestinal inflammation is accompanied by increases in a wide variety of such cytokines and growth factors (reviewed in ref. 1). Since the intestinal epithelium is a frequent target of the inflammatory process in diseases such as Crohn’s disease and ulcerative colitis, it has been logical to examine whether epithelial functions are modulated by cytokines. Indeed, many cytokines and growth factors have been shown to alter a spectrum of epithelial functions (Table 1). Another area of research receiving considerable attention of late is the possibility that the epithelium acts not only as a target of intestinal inflammation, but also as an active participant in the overall inflammatory response. In part this participation may result from the ability of epithelial cells to express adhesion and accessory molecules, and to synthesize inflammatory mediators such as eicosanoids. Both of these properties may be subject to cytokine regulation. Other recent data suggest that the epithelium itself can act as a source of some cytokines. The ability of the epithelium to produce both eicosanoids and proinflammatory cytokines may represent one segment of an autocrine loop whereby inflammatory dysfunction of the epithelium is amplified. This chapter will review recent progress in the area of cytokine-epithelial interactions, with particular reference to the involvement of such interactions in intestinal inflammation. I will draw on the findings of a number of laboratories, as well as our own, to provide an integrated overview of the epithelial functions that may be subject to regulation by cytokines and growth factors.