Figure 4

IL-6 modulates the LPS-stimulated release of IL-1β from glia. Glial cells were treated with LPS)(100 ng/ml) in the presence or absence of rat recombinant IL-6 (20 ng/ml) and cytokine concentrations were assessed at 24 h (A,C) and SOCS3 expression was examined at 90 minutes (B). The LPS-induced release of IL-1β (A; ^*** P < 0.001; ANOVA) was partially inhibited when cells were co-incubated with recombinant IL-6 (A; ⁺ P < 0.05; ANOVA). SOCS3 expression was induced in the presence of LPS (B) and further enhanced when cells were co-treated with LPS and recombinant IL-6 (B). IL-10 production was stimulated by LPS treatment (C; ^*** P < 0.001; ANOVA), an effect that was greater when cells were stimulated with LPS in the presence of recombinant IL-6 (C; ⁺ P < 0.05; ANOVA). Furthermore, inhibition of IL-6 signaling using a neutralizing antibody to the IL-6 receptor (IL-6R) exacerbated the LPS-induced effect on IL-1β release (D; ⁺⁺ P < 0.01; ANOVA) compared to the IgG istoype control antibody while inhibiting the LPS-stimulated release of IL-10 (E; ⁺ P < 0.05; ANOVA). Similarly, when the LPS-stimulated production of IL-6 was inhibited using siRNA targeted against IL-6 (G; ⁺⁺⁺ P < 0.001; ANOVA), the LPS-induced release of IL-1β was enhanced (F; ⁺ P < 0.05; ANOVA), effects that were not apparent in cells that were incubated in the presence of LPS and the non-target (NT) siRNA (F,G).