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, AIDS, and multiple sclerosis (MS), TNF-alpha is produced mainly by cells of the macrophage lineage, which includes microglia in the central nervous system, Here, we describe a mechanism through which TNF-alpha is generated by microglia. We show that activated human T lymphocytes induce 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 expression of CD49d and reduces TNF-beta production, mechanisms which can help account for its efficacy in MS.