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Interleukin‐10, interleukin‐4, and transforming growth factor‐β differentially regulate lipopolysaccharide‐induced production of pro‐inflammatory cytokines and nitric oxide in co‐cultures of rat astroglial and microglial cells

The pro‐inflammatory cytokines interleukin‐1β (IL‐1β), IL‐6, tumor necrosis factor‐α (TNF‐α), and nitric oxide (NO) can be produced by activated glial cells and play a critical role in various neurological diseases. Using primary co‐cultures of rat microglial and astroglial cells, we investigated the effects of the anti‐inflammatory cytokines transforming growth factor‐β1 (TGF‐β1)/β2, IL‐4, and IL‐10 on the production of (pro‐) inflammatory mediators after stimulation of the cells with lipopolysaccharide (LPS; 0.1 μg/ml, 24 h). IL‐10 (10 and 100 ng/ml) and IL‐4 (5 and 50 U/ml) suppressed the LPS‐induced production of NO, IL‐6, and TNF‐α in a dose‐dependent manner, whereas TGF‐β1/β2 (2 and 20 ng/ml) only suppressed NO production. LPS‐induced levels of IL‐1β were suppressed by IL‐10, but not by IL‐4 and TGF‐β1/β2. Conversely, co‐incubation of the glial cells with LPS and antibodies to TGF‐β1/β2 selectively enhanced LPS‐induced NO production, whereas co‐incubation with antibody to IL‐10 enhanced LPS‐induced production of all pro‐inflammatory cytokines and NO. This finding strongly suggests that effective concentrations of TGF‐β1/β2 and IL‐10 are produced by LPS‐stimulated glial cell co‐cultures. Production of IL‐10 in these co‐cultures was confirmed by measurement of rat IL‐10 by radioimmunoassay. We conclude that anti‐inflammatory cytokines affect the production of inflammatory mediators in LPS‐activated co‐cultures of microglial and astroglial cells differentially. GLIA 30:134–142, 2000. © 2000 Wiley‐Liss, Inc.