Interleukin-4 modulates cholinergic neural control of mouse small intestinal longitudinal muscle

Interleukin-4 contributes to expulsion of certain gastrointestinal parasites and causes intestinal mucosal mastocytosis. Because mast cell-derived mediators are spasmogenic, potentially causing parasitic expulsion, we investigated the effect of interleukin-4 on smooth muscle and the mast cell and mediator dependency of this effect. BALB/c, mast cell-deficient W/W-v mice, 5-lipoxygenase-deficient mice, and their littermate controls were injected with interleukin-4-anti-interleukin-4 antibody complexes that chronically increase serum interleukin-4 levels. Mid-small intestinal segments, hung longitudinally in organ baths, were stimulated electrically or by agonists. The cholinergic response to electrical field stimulation was significantly increased by interleukin-4 treatment in BALB/c but not W/W-v mice. The enhanced cholinergic contraction was not due to increased acetylcholine responsiveness but was dependent on leukotriene D-4, since it was reversed by leukotriene D-4 receptor antagonism, and not observed in 5-lipoxygenase knock-out mice. Leukotriene D-4 responsiveness was unaffected by interleukin-4 treatment. We conclude that interleukin-4 amplifies cholinergic excitation through a mast cell and leukotriene D-4-dependent mechanism.