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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 …

BACKGROUND: Elements of the mucosal immune system may play an important part in regulating epithelial barrier function in the intestinal tract. Intraepithelial lymphocytes (IELs) represent a subtype of immunocyte which is strategically placed to regulate epithelial function at most mucosal sites. AIMS AND METHODS: An IEL derived cell line (SC1) was used to examine its effects on the model epithelium T84--a tumour derived cell line which retains the phenotype of colonic crypt cells. Transepithelial electrical resistance (TER) was used as a marker of epithelial integrity. RESULTS: Coculture of T84 cells with SC1 produced a significant fall in TER as did exposure of T84 monolayers to IEL derived supernatant. Recombinant interferon-gamma (rIFN gamma) also reduced TER in T84 monolayers. Cycloheximide prevented the effects of IEL supernatant and of rIFN gamma on TER. The fall in TER in response to rIFN gamma was attenuated by blocking antibodies, which did not alter the fall in resistance induced by IEL supernatant. Fractions of IEL supernatant, separated on the basis of size, evoked temporally distinct changes in TER. Ultrastructural studies support the hypothesis that the slow onset but severe fall in TER indicates catastrophic effects on the monolayer. The more rapid onset fall in TER was not associated with gross changes in monolayer morphology. Reduction of TER by IEL supernatant was not influenced by inhibitors of tyrosine phosphatase or of protein kinase C. Although herbimycin did reduce the rapid onset change in TER, the tyrosine kinase inhibitor genistein did not alter responses to IEL supernatant. CONCLUSIONS: Mucosal T cells may influence barrier function by a process involving new protein synthesis by epithelial cells. This model may have relevance in some inflammatory conditions of the gastrointestinal tract.