The role of microglia in the pathogenesis of the central nervous system

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In this study we aimed to approach the origin and function of microglia, roles of microglia in the cytokine network in the central nervous system (CNS) and in the pathophysiology of CNS disorders. Microglia was shown to be regulated for their proliferation and differentiation by colony stimulating factor as was peripheral macrophages. However, the effects of macrophage-deactivating cytokines such as IL-4, IL-10 and TGFbeta on microglia were different from those on macrophages. All three cytokines suppressed cytokine production by CNS cells. But, IL-4 induced proliferation of microglia but not in macrophages. IL-10 down-regulated the expression cytokine receptors in microglia but not in macrophages. Since we have shown that IL-10 is produced by microglia and astrocytes and the receptors are expressed by these cells, these cytokines may play a role in the CNS cytokine network as a negative regulators, functioning differently from peripheral immune system. We also found that the glial cells produced IL-5 whose functions are as yet unknown.Although a variety of cytokines are produced in the CNS,most of them were induced in the pathological conditions. We only detect IL-1, TNFalpha and M-CSF mRNA in the normal adult brain. We also found the microglia responded to produce cytokine much faster than other glial cells and the cytokine produced by microglia such as TNFalpha or IL-1 induced IL-6 production in astrocytes. Taking altogether, we assume microglia have some different characteristic from macrophages and play a major regulatory role in the cytokine network in the CNS.