Background & aims: The proinflammatory cytokine interferon gamma (IFN-gamma) disrupts epithelial barrier integrity and attenuates secretagogue-induced chloride secretion. This study tested the efficacy of the anti-inflammatory cytokine interleukin 10 (IL-10) in maintaining epithelial barrier and chloride secretory function in the presence of IFN-gamma.
Methods: T84 epithelial cell monolayers were treated with IL-10, IFN-gamma, or IFN-gamma plus IL-10. Monolayer barrier integrity was assessed by measurements of electrical conductance, unidirectional mannitol and inulin fluxes, and tight junctional charge selectivity in Ussing chambers. Short-circuit current (Isc) was measured in response to carbachol and forskolin stimulation.
Results: IL-10 attenuated the IFN-gamma-induced increase in electrical conductance and totally prevented the IFN-gamma-induced increase in mannitol and inulin fluxes. IL-10 did not prevent the IFN-gamma-induced abolishment of tight junctional charge selectivity but did attenuate the total increase in sodium and chloride permeability. IFN-gamma and IL-10 both separately reduced peak forskolin and carbachol-stimulated Isc. IL-10 pretreatment further enhanced the IFN-gamma-induced reduction in secretagogue-induced Isc.
Conclusions: In T84 epithelial monolayers, IL-10 maintains the size, but not the charge, selectivity of the epithelial tight junction in the presence of IFN-gamma. In addition, both IL-10 and IFN-gamma limit carbachol and forskolin-induced increase in Isc.