Role of Gender on the Immune Response During Sepsis

Wednesday, 1 August 2012

Angelita Maria Stabile, RN, MS, PhD
Nátali Artal Padovani, RN
Marcelo Eduardo Batalhão, MS
Evelin Capellari Carnio, RN, MS, PhD
School of Nursing at Ribeirão Preto, São Paulo University, Ribeirão Preto, Brazil

Learning Objective 1: The learner will be able to perceive basic sciences as a tool to the development of new perspectives in nurse research

Learning Objective 2: The learner will be able to have a better understanding of how gender affects the immune response during sepsis and septic shock

Purpose: Septic shock remains the main cause of mortality in intensive care units. Nitric oxide (NO) is related to the pathogenesis of sepsis due to its vasodilator and cytotoxic actions. One significant finding in clinics is that man and woman respond differently to sepsis, with better prognosis related to women. This study was designed to investigate the role of gender on immune response in an experimental model of septic shock.

 Methods: In the first set of experiments (in vivo) male and female rats were injected intraperitoneally (IP) for three consecutive days with estradiol cypionate (ECP), 40µg/kg or vehicle. In the third day, after ECP injection, rats receive IP injection of 10mg/kg of bacterial lipopolysaccharide (LPS) or saline solution. Plasma was collected 2 and 4 hours after LPS. In the second set of experiments (in vitro), macrophage culture was performed from peritoneal wash of male and female rats. Culture was stimulated with β-estradiol (10-9M) and LPS 1µg/ml and medium collected 12 and 24 hours after stimulation. NO was measured in samples of both sets of experiments.

Results: In vivo experiments showed that administration of LPS increased NO plasma concentration in males and females. ECP pre-treatment decreased NO concentration in females in the two studied periods; conversely, had no effect in males. Results of in vitro experiments showed that macrophages from males produced more NO than the ones from female, either in basal conditions or after LPS stimulation; however, treatment of the culture with β-estradiol, significantly increased the NO production in macrophages from male but had no effect in female rats.

 Conclusion: Our results indicate that estradiol may have pro or anti-inflammatory actions depending on the gender; however, estradiol in female seems to be protective, since it decreased NO plasma concentration. These results may explain in part the better outcomes of woman during sepsis.