IL-4 DIRECTLY MODULATES FUNCTION OF A MODEL HUMAN INTESTINAL EPITHELIUM

Intestinal epithelia are in intimate contact with subepithelial and in traepithelial lymphocytes. When stimulated, mucosal lymphocytes genera te inflammatory cytokines such as IL-4 and IFN-gamma. We have shown th at IFN-gamma directly regulates epithelial function. It is unknown whe ther IL-4 might influence epithelial function and, ii so, whether such influences are similar to or differ from those exerted by IFN-gamma. In this study, we examine the effect of human IL-4 on barrier function , ion transport, and immune accessory ligand expression on T84 cells, a crypt-like epithelial cell line. Basolateral exposure of epithelial monolayers to IL-4 attenuated epithelial barrier function by greater t han 65% in a dose (50% of effective dose = 1 U/ml)- and time (t(1/2) = 24 h)-dependent fashion, and was inhibitable by neutralizing anti-IL- 4 and anti-IL-4R Ab. Stimulated Cl- secretion, as measured by epitheli al short circuit current, was diminished by as much as 70% by IL-4. Ep ithelial preexposure to IL-4 brought about a greater than twofold incr ease in beta(2) integrin-dependent neutrophil adhesion to epithelia, b ut retarded neutrophil migration into and across epithelial monolayers . ELISAs revealed that epithelial exposure to IL-4 had no effect on ce ll surface expression of MHC class I, MHC class II, or ICAM-1. These r esults indicate that IL-4, like IFN-gamma, may serve to regulate intes tinal epithelial function, but that resulting phenotypes may be cytoki ne specific. We speculate from these data that activation of the basol ateral receptor for IL-4 potentially provides a new strategy for dampi ng the cellular component of active inflammation in the intestine.