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Interleukin‐4 and interleukin‐10 regulate IL1‐β induced mouse primary astrocyte activation: A comparative study
Author(s) -
Pousset F.,
Cremona S.,
Dantzer R.,
Kelley K.,
Parnet P.
Publication year - 1999
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199903)26:1<12::aid-glia2>3.0.co;2-s
Subject(s) - astrocyte , interleukin , cytokine , biology , dexamethasone , endocrinology , medicine , glucocorticoid , agonist , interleukin 6 , receptor , immunology , biochemistry , central nervous system
The pro‐inflammatory cytokine interleukin‐1β (IL‐1β) is strongly expressed during brain injury and is able to induce severe cellular brain damage 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, we describe the sequential effects of IL‐4 and IL‐10 on the production of interleukin‐6 (IL‐6) induced by IL‐1β in mouse primary astrocytes and compare these effects to those of the synthetic glucocorticoid agonist, dexamethasone. IL‐6 secretion and IL‐6 mRNA expression were determined by ELISA assay and a comparative RT‐PCR method, respectively. Incubation of mouse astrocytes in primary culture simultaneously with IL‐1β (10 ng/ml) + IL‐10 (10 ng/ml) or IL‐1β + dexamethasone (10 −6 M) markedly reduced IL‐1β 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‐1β. In contrast, after 24 h of IL‐1β treatment, the level of IL‐6 was decreased below constitutive levels, and this change was reversed by addition of IL‐4. IL‐6 production in IL‐1β pretreated cells was also increased by addition of IL‐4, whereas IL‐10 and dexamethasone had no effects. The delayed time dependent effect of IL‐4 might be partially explained by the induction of IL‐4 receptor α‐chain mRNA expression by IL‐1β. Therefore, we conclude that IL‐10 and dexamethasone have rapid immunosuppressive effects on the astrocyte response to IL‐1β stimulation, whereas IL‐4, which has a delayed action, acts as an immune inducer. GLIA 26:12–21, 1999. © 1999 Wiley‐Liss, Inc.