Female sex hormones modulate the function of LPS-treated macrophages

Problem: To study the effects of estradiol (E₂) or progesterone on macrophage function in the presence of lipopolysaccharide (LPS). Method of study: Male rat peritoneal macrophages were treated in vitro with 0.1 μg/mL of LPS and E₂ or progesterone. Results: At 10^-2 ng/mL, E₂ significantly (P < 0.05; n = 6) enhanced tumor necrosis factor (TNF) release by LPS-treated macrophages. TNF release was significantly (P < 0.05; n = 6) inhibited by 10² ng/mL or 10³ ng/mL of E₂ and by progesterone at less than 10^-3 ng/mL or greater than 10^-1 ng/mL. E₂ (10^-4 and 10 ng/mL) and progesterone (1^-6-10^-4 ng/mL and 10² ng/mL) each significantly (P < 0.05, n = 8) enhanced H₂O₂ release by LPS-treated macrophages. E₂ (< 10^-2 and > 10 ng/mL) and progesterone (10^-7-10⁴ ng/mL) each significantly inhibited (P < 0.05; n = 6) NO₂^- release by LPS-treated macrophages. Conclusions: Exposure to LPS tended to diminish the effects of E₂ and to enhance the effects of progesterone on the parameters determined here. Such LPS-associated alterations in the dose-response profile of macrophages to female sex hormones may contribute to gender-related differences in the immune response under normal and pathological conditions.