Sex Differences in Sepsis Survival Involve Effects of Gonadal Steroid Hormones

Abstract

Sepsis is one of the leading causes of death in human non‐coronary induced intensive care cases; in the United States, more than 750,000 people are diagnosed with sepsis each year, and 20 to 30% of those die from severe sepsis. While advances in aggressive supportive care have resulted in a reduction in the number of deaths from sepsis each year, the total number of cases of sepsis continues to increase. Given the complexity and severity of sepsis, more successful treatment will require thorough elucidation of the various inflammatory mechanisms. Thus, in the present study, sex differences in sepsis survival and the role(s) of the gonadal steroid hormones were studied. Age‐matched male (M) and female (F) Sprague‐Dawley rats (12–14 wks age) either remained intact (InT) or were gonadectomized (GnX) using standard surgical methods. Four weeks later, sepsis was induced in InT (N = 7) and GnX (N = 3) M and F rats using standard cecal ligation and puncture (CLP) methods while under isoflurane anesthesia (50% of cecum ligated, single bilateral puncture, 20 ga hypodermic needle). Immediately after CLP, rats were resuscitated with 40 ml/kg warmed (37°) saline, given a single dose of buprenorphine SR (1.0 mg/kg), and mortality was monitored over the following 10 days. A separate group of InT M and F rats underwent sham CLP surgery. Kaplan‐Meier analysis of the data revealed that survival was 100% in both M and F sham groups. In InT CLP groups, by day 3, there was a drastic reduction in survival to 42.8% in M but 57.1% in F; this sex difference increased over time and by day 6, maximal survival was 14.3% in M but 42.8% in F. In GnX, at day 3, survival declined to 33% in M, but increased to 100% in F. These data suggest that prominent sex differences exist in survival from CLP‐induced sepsis, which may involve effects of the gonadal steroid hormones on inflammatory and immune function in M vs. F rats.Support or Funding Information(State of Texas)