BACKGROUND & AIMS: It has been proposed that the anti-inflammatory cytokine interleukin (IL)-10 might be an effective therapeutic agent in the treatment of inflammatory bowel disease. This study examined the effects of human recombinant IL-10 on ileal sodium and chloride transport in Sprague-Dawley rats. METHODS: Unidirectional fluxes of sodium and chloride and tissue electrical parameters were measured under voltage-clamped conditions in ussing chambers. Intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) were measured in isolated enterocytes. RESULTS: Jejunal and ileal tissue responded to serosal addition of IL-10 with a transient decrease in short-circuit current reflecting an IL-10-induced increase in net sodium and chloride absorption because of an increase in mucosal to serosal ion movement. The IL-10-induced absorption was not prevented by tetrodotoxin but did show tachyphylaxis. IL-10 reversed, or markedly attenuated, forskolin- and carbachol-induced net chloride secretion. The effects of IL-10 on net secretion were accompanied by a reduction in forskolin-stimulated cAMP levels and a decrease in basal cAMP levels. An additional effect of IL-10 was its induction of bicarbonate secretion only in the presence of secretagogues. CONCLUSIONS: This study shows that IL-10 enhances intestinal electroneutral sodium and chloride absorption, inhibits stimulated chloride secretion, and under some secretory conditions stimulates bicarbonate secretion.
BACKGROUND & AIMS: It has been proposed that the anti-inflammatory cytokine interleukin (IL)-10 might be an effective therapeutic agent in the treatment of inflammatory bowel disease. This study examined the effects of human recombinant IL-10 on ileal sodium and chloride transport in Sprague-Dawley rats. METHODS: Unidirectional fluxes of sodium and chloride and tissue electrical parameters were measured under voltage-clamped conditions in ussing chambers. Intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) were measured in isolated enterocytes. RESULTS: Jejunal and ileal tissue responded to serosal addition of IL-10 with a transient decrease in short-circuit current reflecting an IL-10-induced increase in net sodium and chloride absorption because of an increase in mucosal to serosal ion movement. The IL-10-induced absorption was not prevented by tetrodotoxin but did show tachyphylaxis. IL-10 reversed, or markedly attenuated, forskolin- and carbachol-induced net chloride secretion. The effects of IL-10 on net secretion were accompanied by a reduction in forskolin-stimulated cAMP levels and a decrease in basal cAMP levels. An additional effect of IL-10 was its induction of bicarbonate secretion only in the presence of secretagogues. CONCLUSIONS: This study shows that IL-10 enhances intestinal electroneutral sodium and chloride absorption, inhibits stimulated chloride secretion, and under some secretory conditions stimulates bicarbonate secretion.