Sex differences in IL-10's anti-inflammatory function: greater STAT3 activation and stronger inhibition of TNF-α production in male blood leukocytes ex vivo

Intorleukin-10 (IL-10) inhibits proinflammatory cytokine production in blood leukocytes an effect mediated by signal transducer and activator of transcription 3 (STAT3) activation. To examine potential sex-based differences in IL-10's anti-inflammatory function, we treated whole blood from healthy males and females (n = 16 participants of each sex; age: 28 +/- 6 yr; body mass index: 23.5 +/- 2.3 kg/m(2)) with increasing concentrations of IL-10 (1-100 ng/mL) and quantified changes in phosphorylated STAT3 (pSTAT3) in CD14(+) monocytes and CD4(+) lymphocytes via flow cytometry. In parallel, liposaccharide (LPS)-stimulated whole blood cultures were used to assess sex-based differences in IL-10's ability to inhibit tumor necrosis factor (TNF)-alpha production. IL-10 concentration dependently increased pSTAT3 median fluorescent intensity (MA) in CD14(+) and CD4(+) cells (main effects of concentration, P < 0.01) with males exhibiting larger changes in pSTAT3 MFI in both cell types (main effects of sex, P < 0.01). Accordingly, IL-10-mediated inhibition of TNF-alpha production was more pronounced in males (main effect of sex, P < 0.01) with changes in other monocyte-derived cytokines (IL-1 beta, IL-1RA, and IL-15) also supporting a sexual dimorphism in IL-10 action (P < 0.05). These sex-based differences were not explained by differences in circulating plasma IL-10 concentrations, basal IL-10 receptor expression in unstimulated CD14(+) and CD4(+) cells, nor the basal expression of IL-10 signaling proteins (STAT3, SHIP1, and p38 MAPK) in unstimulated peripheral blood mononuclear cells. We conclude that IL-10's antiinflammatory function differs between male and female blood leukocytes ex vivo. This sexual dimorphism should be considered in future work investigating IL-10's anti-inflammatory action in humans as it may represent a mechanism contributing to sex differences in overall immune function.

Automated summary

There are sex-based differences in the anti-inflammatory function of IL-10 observed in ex vivo blood leukocytes, with males exhibiting larger changes in pSTAT3 levels and a more pronounced inhibition of TNF-alpha production by IL-10. These findings suggest that sex differences in IL-10 action may contribute to overall sex differences in immune function.