Actions of exogenous and endogenous IL-10 on glial responses to bacterial LPS/cytokines

The objective of this study was to investigate the actions of exogenous and endogenous IL-10 on inflammatory responses of glia. Studies were conducted in primary, mixed glial cultures from C57BL/6 (wild-type [WT]) and IL-10-deficient C57BL/6 (IL-10 knockout [KO]) neonatal mice. Activation of cultures from WT mice by bacterial lipopolysaccharide (LPS, 10 ng/ml-10 μg/ml, 24 h), caused dose-dependent increases in nitric oxide (NO) and prostaglandin E2 (PGE2) release. In cultures from IL-10 KO mice, LPS elicited markedly attenuated release of NO (approximately 4-fold) and PGE2 (approximately 17-fold). In WT cultures, co-incubation with IL-10 (10 or 100 ng/ml, 24 h) inhibited the effects of LPS on release of NO (30%) and PGE2 (40-50%). In cultures from IL-10 KO mice, the addition of IL-10 (10 or 100 ng/ml, 24 h) completely abolished LPS-induced NO and PGE2 release. LPS did, however, release of IL-1β and TNF-α in cultures from all animals. Co-incubation of WT cultures with IL-10 (1, 10, or 100 ng/ml, 24 h) dose-dependently reduced the release of IL-1β (by 0%, 15%, 75%, respectively). In cultures from IL-10 KO mice, co-incubation with IL-10 (1, 10, or 100 ng/ml, 24 h) completely abolished LPS induced release of IL-1β. Co-incubation with IL-10 (1, 10, 100 ng/ml) reduced, LPS-induced TNF-α release dose-dependently in WT cultures (by 15%, 50% and 90%) and abolished LPS-induced TNF-α release in cells from IL-10 KO mice. These results indicate that in glia from WT mice, exogenous IL-10 attenuates LPS-induces release of NO, PGE2, TNFα and IL-1β. In contrast, mixed glial cultures from IL-10 KO mice showed reduced responses to LPS, but increased sensitivity to exogenous IL-10. © 2001 Wiley-Liss, Inc.