Interleukin-4 and interleukin-10 regulate IL1-beta induced mouse primary astrocyte activation: A comparative study

The pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) is strongly ex pressed during brain injury and is able to induce severe cellular brain dam age via the production of soluble factors. Different processes regulate IL- 1 biological activities, like the production of anti-inflammatory cytokines such as interleukin-4 (IL-4) and interleukin-10 (IL-10). In this report, w e describe the sequential effects of IL-4 and IL-10 on the production of in terleukin-6 (IL-6) induced by IL-1 beta in mouse primary astrocytes and com pare these effects to those of the synthetic glucocorticoid agonist, dexame thasone. IL-6 secretion and IL-6 mRNA expression were determined by ELISA a ssay and a comparative RT-PCR method, respectively. Incubation of mouse ast rocytes in primary culture simultaneously with IL-1 beta (10 ng/ml) + IL-10 (10 ng/ml) or IL-1 beta + dexamethasone (10(-6) M) markedly reduced IL-1 b eta induced IL-6 secretion and IL-6 mRNA expression, respectively, whereas simultaneous addition of IL-4 (10 ng/ml) did not alter the induction of IL- 6 by IL-1 beta. In contrast, after 24 h of IL-1 beta treatment, the level o f IL-6 was decreased below constitutive levels, and this change was reverse d by addition of IL-4. IL-6 production in IL-1 beta pretreated cells was al so increased by addition of IL-4, whereas IL-10 and dexamethasone had no ef fects. The delayed time dependent effect of IL-4 might be partially explain ed by the induction of IL-4 receptor alpha-chain mRNA expression by IL-1 be ta. Therefore, we conclude that IL-10 and dexamethasone have rapid immunosu ppressive effects on the astrocyte response to IL-1 beta stimulation, where as IL-4, which has a delayed action, acts as an immune inducer. GLIA 26:12- 21, 1999. (C) 1999 Wiley-Liss, Inc.