IL-10 PRODUCTION BY ADULT HUMAN-DERIVED MICROGLIAL CELLS

Microglia, a population of central nervous system (CNS) macrophages, h ave been demonstrated to support immune accessory and effector functio ns in the CNS. Numerous studies support the role of microglia in CNS d evelopment and pathology, where activation of microglia is consistentl y noted. The current study investigated microglial immune functions un der basal and activation conditions and assessed the ability of interl eukin-10 (IL-10), added exogenously or produced by microglia, to down- regulate microglial functions. This report demonstrates that microglia from the adult human brain produce IL-10 following interferon-gamma/l ipopolysaccharide activation. Functionally, recombinant human IL-10 do wn-regulated basal HLA-DR expression by microglia and inhibited, in a dose-dependent response, the ability of microglia to stimulate CD4(+) T-cells in antigen presentation assays. These data, together with rece nt observations of the inhibition of experimental allergic encephalomy elitis (EAE) following IL-10 administration and reduced CNS infection by Listeria monocytogenes after anti-IL-10 treatment, suggest that IL- 10 production by microglia may have important immune-regulatory functi ons in CNS disease and disease models. Copyright (C) 1996 Elsevier Sci ence Ltd.