Estrogen inhibits lipopolysaccharide-induced tumor necrosis factor-α release from murine macrophages

During their reproductive years, females have a lower risk for atherosclerosis as compared with age-matched males, although the mechanism behind this are not clearly understood. Cytokines, including TNF-alpha, play an important role in the pathogenesis of atherosclerosis. We therefore evaluated whether or not there was any difference between 17 beta -estradiol and testosterone in modulating TNF-alpha release from murine bone marrow-derived macrophages (BMM) in vitro. Cells were incubated with or without physiological concentrations (10(-10)-10(-8) M) of 17 beta -estradiol or testosterone for 48 h, followed by an additional 6 h in the absence or presence of lipopolysaccharide (LPS: 10 mug/ml). The amount of TNF-alpha released into the culture medium was determined with radioimmunoassay. We found that 17 beta -estradiol or testosterone alone did not affect TNF-alpha release from BMM as compared to untreated controls. Preincubation with 17 beta -estradiol significantly inhibited LPS-induced TNF-alpha release by 18.15% (P<0.05), 25.28% (p<0.05) and 40.93% (p<0.01) for 10(10), 10(9) and 10(8) M of 17-estradiol, respectively, as compared to LPS alone. In contrast, testosterone tested for 3 concentrations did not significantly effect TNF-alpha release induced by LPS. The results indicate that 17 beta -estradiol, but not testosterone, inhibits TNF-alpha release from LPS-stimulated macrophages, which may be one of the mechanisms by which estrogen protects against atherosclerosis. (C) 2001 Prous Science. All rights reserved.