Interactions between Gender and Sepsis-Implications for the Future

Abstract

Sex and gender dimorphisms are found in a large variety of diseases, including sepsis and septic shock which are more prevalent in men than in women. Animal models show that the host response to pathogens differs in females and males. This difference is partially explained by sex polarization of the intracellular pathways responding to pathogen-cell receptor interactions. Sex hormones seem to be responsible for this polarization, although other factors, such as chromosomal effects, have yet to be investigated. In brief, females are less susceptible to sepsis and seem to recover more effectively than males. Clinical observations produce more nuanced findings, but men consistently have a higher incidence of sepsis, and some reports also claim higher mortality rates. However, variables other than hormonal differences complicate the interaction between sex and sepsis, including comorbidities as well as social and cultural differences between men and women. Conflicting data have also been reported regarding sepsis-attributable mortality rates among pregnant women, compared with non-pregnant females. We believe that unraveling sex differences in the host response to sepsis and its treatment could be the first step in personalized, phenotype-based management of patients with sepsis and septic shock.

Keywords: gender; infection; sepsis; sex; shock.

Figure 1

In males (top panel), sepsis induces severe cardiac dysfunction by activating pathways responsible for inflammation, apoptosis, oxidative stress and by inhibiting pathways associated with excitation/contraction coupling (indications in red). Landiolol, by acting on the regulation of numerous genes, strongly improves cardiac function by reversing these biological processes (blue indications). In females (bottom panel), the effect of sepsis is markedly weaker than in males and the cardiac dysfunction is much more pronounced (indications in red). In contrast to the male, landiolol has little effect on gene regulation. It does not improve the effect of sepsis on biological processes such as inflammation or oxidative stress but, on the contrary, acts on the beta-adrenergic pathway and further decreases the contraction and relaxation capacity of the heart (blue indications). Cellular pathways according to sex. + = activation; − = inhibition; = increase; = decrease; red rectangle = upregulated gene; green rectangle = downregulated gene.