Sex differences in inflammatory cytokines and CD99 expression following in vitro lipopolysaccharide stimulation

Sex influences the severity and evolution of various inflammatory conditions. Although many studies have demonstrated the role of sex hormones in immune response modulation, recent clinical data revealed significant sex differences in inflammatory markers in prepubertal children, suggesting a genetic contribution. We studied several immune functions depending on X-linked genes in healthy adults of both sexes: the respiratory burst of purified neutrophils, the CD99 and CD11b expression of stimulated leukocytes as markers of adhesion and diapedesis, and the production of inflammatory cytokines in whole blood after incubation with lipopolysaccharide for 24 h. The percentage of monocytes expressing CD99 was higher in men than in women, thus confirming the higher CD99 expression reported in males using reverse transcription-polymerase chain reaction. In addition, we observed a higher tumor necrosis factor α and tendency toward higher interleukin (IL) 6 production in men after lipopolysaccharide stimulation. These differences may contribute to the higher mortality reported in men with septic shock. Tumor necrosis factor α production significantly correlated with monocyte count, with men having a higher monocyte count than women. When cytokine levels were normalized to monocyte counts, a higher IL-8 production was found in women, which may explain the higher neutrophil count observed in girls with acute inflammatory diseases, because IL-8 is a major neutrophil chemoattractant. These sex differences regarding the activation of certain X-linked genes involved in innate immunity confirm our clinical observations, thus supporting the role of sex chromosomes in inflammatory response.