Role for IL-4 in macromolecular transport across human intestinal epithelium

Increased epithelial permeability is associated with intestinalinflammation, but there is little information on factors that regulatebarrier function in the absence of or before inflammation. We examinedif interleukin (IL)-4, or serum from atopic individuals, could alterthe barrier function of human colonic epithelial (T84) monolayers toantigenic-sized macromolecules. IL-4 and atopic serum significantlydecreased T84 monolayer resistance and increased transepithelialhorseradish peroxidase (HRP) transport. Bidirectional transport studiesdemonstrated that IL-4 selectively enhanced apical-to-basal movement ofHRP. HRP transport induced by IL-4 was inhibited by cold (4°C) andthe tyrosine kinase inhibitor genistein, but not the protein kinase Cinhibitor staurosporine. Electron microscopic analysis demonstratedthat both transcellular and paracellular pathways were affected.Anti-IL-4 antibodies abolished the increase in HRP transport inresponse to both IL-4 and serum. We speculate that enhanced productionof IL-4 in allergic conditions may be a predisposing factor toinflammation by allowing uptake of luminal antigens that gain access tothe mucosal immune system.