Gender differences in cytokine secretion by human peripheral blood mononuclear cells: Role of estrogen in modulating LPS-induced cytokine secretion in an ex vivo septic model

Clinical studies demonstrate a better outcome of sepsis in females. Elevate d estrogen levels and plasma cytokine imbalance occur in septic patients. W e propose that gender-different cytokine secretion by the peripheral blood mononuclear cells (PBMCs) in sepsis determines the clinical outcome. A 2 x 10(6) PBMC sample from healthy volunteers (10 males and 10 females) was inc ubated with 1 ng/mL of lipopolysaccharide (LPS), estradiol (E-2; 0, 0.03, 0 .3, 3.0, 30 ng/mL), or 1 ng/mL of LPS + E-2 (0, 0.03, 0.3, 3.0, 30 ng/ml), and supernatant cytokine levels were measured. Tumor necrosis factor alpha (TNF alpha) and interleukin (IL)-6 production by PBMCs from both sexes was time-dependently stimulated by LPS. At 6 h after LPS challenge, the TNF alp ha level of male PBMCs was significantly higher but IL-6 secretion by femal e PBMCs was higher (two-way ANOVA: P<0.05). E-2 alone stimulated cytokine s ecretion by male PBMCs. Addition of the same E-2 concentration as in sepsis patients' plasma modulated LPS-induced cytokine production. No significant sex differences in LPS-stimulated TNF<alpha> or IL-6 secretion by PBMCs we re found, but IL-10 secretion by male PBMCs was significantly suppressed. T his study demonstrated a gender difference in PBMCs responsiveness to LPS a nd E-2 stimulation and E-2-modulated cytokine secretion. In this PBMCs mode l of sepsis, only the supernatant IL-10 level was significantly lower in ma les. These ex vivo findings may partially explain the mechanism underlying the poorer outcome of male sepsis patients.