CRITICAL ROLE FOR IL-4 IN REGULATING DISEASE SEVERITY IN EXPERIMENTALALLERGIC ENCEPHALOMYELITIS AS DEMONSTRATED IN IL-4-DEFICIENT C57BL 6 MICE AND BALB/C MICE/

Experimental allergic encephalomyelitis (EAE) is a T cell-mediated aut oimmune disease of the central nervous system (CNS) that has served as the principal experimental model for multiple sclerosis (MS), Suscept ibility to disease is thought to correlate with the ability to generat e a Th1-type cytokine profile in myelin-responsive T cells, whereas T cells producing a Th2 cytokine pattern, in particular IL-4, are though t to be nonencephalitogenic and also to confer protection against a Th 1-type response. However, recent studies using a variety of geneticall y engineered animals in which the genes for Th1-type cytokines and/or their receptors have been inactivated have called into question the Th 1-Th2 paradigm in experimental allergic encephalomyelitis. In this rep ort we have addressed the contribution of IL-4 to disease expression b y studying two strains of mice, C57BL/6 and BALB/c, in which the gene for IL-4 has been inactivated. The IL-4-deficient C57BL/6 mice, and to a lesser extent the IL-4-deficient BALB/c mice, developed a more seve re form of clinical disease, a more extensive pathologic involvement o f the spinal cord, and an increased expression of proinflammatory cyto kines in the CNS than their wild-type littermates. BALB/c and C57BL/6 mice showed a slightly different cytokine profile in the CNS, Both gro ups of animals recovered from the acute clinical episode in a time fra me that was essentially identical to that found in the wild-type contr ols. We conclude that IL-4 plays an important role in modulating the s everity of the encephalitogenic process, but does not by itself contri bute to spontaneous remission from the disease.