Cytokine regulation of epithelial permeability and ion transport

The intestinal epithelium serves as a dynamic barrier which, in the course of its normal function, maintains regulated uptake of nutrients and water at the same time as excluding potential pathogens. Enteropathies, including inflammatory bowel disease (IBD) result in, or perhaps even from, perturbed epithelial function. Despite the idiopathic nature of IBD, it is apparent that much of the pathophysiology, tissue damage and symptomatology of these disorders are due to inappropriate or exaggerated immune reactions.1 2 Cytokines are, inter alia, regulators of both innate and acquired immunity, so therefore it is not surprising that exaggerated effects of cytokines in acute or chronic inflammatory states may be due to unregulated production of pro-inflammatory cytokines or inadequate synthesis of anti-inflammatory cytokines. Indeed, increases in cytokine concentrations in models of enteric inflammation or IBD are well documented.3 Here, we provide an overview of cytokine regulation of epithelial ion transport and permeability, highlighting, where appropriate, the potential of the epithelium to modulate mucosal immune reactions and its own function. Relatively few studies have demonstrated cytokine effects on epithelial function in vivo or by examining intestinal tissue responses ex vivo.4 5 Several features contribute to difficulties with interpretation of such studies. Firstly, cytokines act in a coordinated interplay of often redundant, pleiotropic and occasionally opposing actions.6 Secondly, given the complex intercellular signalling that occurs within the gut,7cytokine effects may involve other, non-cytokine mediators.8-10 Finally, virtually every putative mediator of inflammation has been implicated in diseases of the intestine, representing at one time the academic pharmacologist’s dream and the therapist’s nightmare. The advent of epithelial cell lines, principally the tumour derived T84, Caco-2 and HT-29 cell lines, has offered opportunities to study influences of cytokines on epithelial function by taking a reductionist approach. These cell lines, when grown on …