The role of IL-4 in Heligmosomoides polygyrus-induced alterations in murine intestinal epithelial cell function

IL-4 and IL-13 promote gastrointestinal worm expulsion, at least in part, t hrough effects on nonlymphoid cells, such as intestinal epithelial cells. T he role of IL-4/IL-13 in the regulation of intestinal epithelial function d uring Heligmosomoides polygyrus (Hp) infection was investigated in BALB/c m ice infected with Hp or treated with a long-lasting formulation of recombin ant mouse IL-4/alpha IL-4 complexes (IL-4C) for 7 days. Separate groups of BALB/c mice were drug-cured of initial infection and later reinfected and t reated with anti-IL-4R mAb, an antagonist of IL-4 and IL-13 receptor bindin g, or with a control mAb. Segments of jejunum were mounted in Ussing chambe rs, and short circuit current responses to acetylcholine, histamine, seroto nin, PGE(2), and glucose were determined. Although only modest changes in e pithelial cell function were observed during primary Hp infection, IL-4C or a secondary Hp infection each induced more dramatic changes, including inc reased mucosal permeability, reduced sodium-linked glucose absorption, and increased Cl- secretory response to PGE(2). Some, but not all, effects of I L-4C and Hp infection were dependent on enteric nerves. Hp-induced changes in epithelial function were attenuated or prevented by anti-IL-4R mAb. Thus , IL-4/IL-13 mediate many of the effects of Hp infection on intestinal epit helial cell function and do so both through direct effects on epithelial ce lls and through indirect, enteric nerve-mediated prosecretory effects. Thes e immune system-independent effector functions of IL-4/IL-13 may be importa nt for host protection against gastrointestinal nematodes.