Human monocytes respond to lipopolysaccharide (LPS) stimulation in a sex-dependent manner

Monocytes play a critical role in inflammation and immune response, their activity being sex-dependent. However, the basis of sex differences is not well understood. Therefore, we investigated the lipopolysaccharide (LPS) effects on tumor necrosis factor-α (TNF-α) release, autophagy, and chemotaxis in freshly isolated monocytes from healthy young men and women. In basal conditions, male and female monocytes had similar TNF-α release, chemotaxis, and estrogen receptors (ER-α) and ER-β expression, while the LC3II/I ratio was significantly higher in males. LPS treatment induced qualitative and quantitative sex differences. It reduced autophagy and increased TNF-α release only in male monocytes, while, chemotaxis was significantly influenced only in female cells. Moreover, it reduced the expression of ER-α only in female cells, while ER-β expression was reduced in both sexes, but more markedly in female cells. Finally, the interplay between LPS treatment and 17-β-estradiol (E₂ ) was present only in female cells. Globally, these findings expand the concept that sex plays a role in regulating monocytes' functions, being sex differences cell- and parameter-specific.