INTERLEUKIN-4 IN INFLAMMATORY BOWEL-DISEASE AND MUCOSAL IMMUNE REACTIVITY

Background & Aims: Interleukin (IL) 4 has immunoregulatory and anti-in flammatory activities, but little is known about IL-4 in the human gut , We investigated production of IL-4 by isolated lamina propria mononu clear cells (LPMCs) from normal and inflamed intestine and its capacit y to modulate local immune responses, Methods: IL-4 levels were measur ed by enzyme-linked immunosorbent assay in cultures of control and inf lammatory bowel disease LPMCs, and the effect of IL-4 on LPMC prolifer ation and interaction with IL-2, IL-1 beta, lipopolysaccharide, bacter ial antigens, superantigen, and antibodies to various T-cell receptors was investigated, Results: Various stimuli induced LPMCs to produce I L-4, but inflammatory bowel disease cells expressed IL-4 messenger RNA and secreted protein in significantly lower amounts than control cell s, IL-4 failed to stimulate proliferation by fresh LPMCs, but a vigoro us dose-dependent response was observed after preactivation by phytohe magglutinin, IL-2, or IL-4, When added to fresh LPMCs, IL-4 inhibited IL-2-induced proliferation, IL-4 amplified proliferation to IL-1 beta, lipopolysaccharide, peptidoglycan-polysaccharide complexes, staphyloc occus enterotoxin A, and antibodies to the CD3 and CD28 receptors but not to tetanus toroid, Conclusions: Decreased production of IL-4 in in flammatory bowel disease may cause defective immunosuppressive and ant i-inflammatory mechanisms and may contribute to disease pathogenesis. The ability of IL-4 to differentially modulate LPMC reactivity probabl y influences mucosal immune homeostasis.