MICROGLIAL PRODUCTION OF TNF-ALPHA IS INDUCED BY ACTIVATED T-LYMPHOCYTES - INVOLVEMENT OF VLA-4 AND INHIBITION BY INTERFERON-BETA-1B

TNF-alpha is a proinflammatory cytokine involved in many inflammatory conditions such as Crohn's disease, rheumatoid arthritis, cachexia, AI DS, and multiple sclerosis (MS), TNF-alpha is produced mainly by cells of the macrophage lineage, which includes microglia in the central ne rvous system, Here, we describe a mechanism through which TNF-alpha is generated by microglia. We show that activated human T lymphocytes in duce the microglial production of TNF-alpha, and that is attenuated by a functional blocking antibody to CD49d, the alpha chain of the VLA-4 integrin on T cells, We also report that interferon beta-1b (IFN beta -1b), a drug that alleviates symptoms in MS, downregulates the express ion of CD49d and reduces TNF-beta production, mechanisms which can hel p account for its efficacy in MS.