Sexual dimorphism during LPS-induced systemic inflammation

Incidence and outcomes of systemic inflammatory diseases, such as sepsis, differ between men and women, but the underlying mechanisms remain unclear. We examined systemic inflammatory responses in 56 male and 54 female healthy volunteers challenged with 1 ng/kg bacterial lipopolysaccharide (LPS) twice, with an interval of one week. Sex hormones, inflammatory markers, and monocyte RNA expression were determined. Women exhibited higher levels of several proinflammatory mediators than men during the first LPS challenge (TNF +45%, p=0.002; IL-6 +43%, p=0.0009; IP-10 +58%, p<0.0001; G-CSF +60%, p=0.02). Among women, use of hormonal contraceptives was associated with a more pronounced pro-inflammatory response (TNF +60%, p=0.001; IL-8 +30%, p=0.008; IP-10 +37%, p<0.0001). Endogenous concentrations of estrogens and testosterone inversely correlated with the extent of cytokine responses in women, while estrone positively correlated with these responses among men. The magnitude of endotoxin tolerance, exemplified by a significantly blunted cytokine response upon the second LPS challenge, was similar between the sexes, as were monocyte RNA expression patterns. In conclusion, our data indicate that there is considerable sexual dimorphism in systemic inflammation and implicate an important role for sex hormones in regulating immunity.