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

• Published in: Glia 1999-03, Vol.26 (1), p.12-21
• Main Authors: Pousset, F., Cremona, S., Dantzer, R., Kelley, K., Parnet, P.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; astrocyte; Astrocytes - cytology; Astrocytes - drug effects; Astrocytes - physiology; Biological and medical sciences; Brain - cytology; Brain - physiology; Cells, Cultured; Cytokines - biosynthesis; Cytokines - genetics; dexamethasone; Dexamethasone - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - immunology; Glucocorticoids - pharmacology; Humans; IL-1; IL-10; IL-4; IL-6; Interleukin-1 - pharmacology; Interleukin-10 - pharmacology; Interleukin-4 - genetics; Interleukin-4 - pharmacology; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Isolated neuron and nerve. Neuroglia; Kinetics; Life Sciences; Lipopolysaccharides - pharmacology; Mice; mouse; Receptors, Interleukin - genetics; Receptors, Interleukin-10; Receptors, Interleukin-4 - genetics; Recombinant Proteins - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Transcription, Genetic - immunology; Vertebrates: nervous system and sense organs
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/(SICI)1098-1136(199903)26:1<12::AID-GLIA2>3.0.CO;2-S

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.