Sepsis-induced cardiac dysfunction: Gender bias role of allograft inflammatory factor-1

Sepsis-induced cardiac dysfunction is a major contributor to the high morbidity and mortality rates seen in septic patients, with those suffering from concurrent cardiac dysfunction experiencing mortality rates up to 90 %. This study elucidates the role of allograft inflammatory factor-1 (AIF-1) in sepsis-induced cardiac dysfunction, using a cecal ligation and puncture (CLP) model in both wild-type (WT) and AIF-1 knockout (^-/-) C57BL/6 mice. We specifically examined AIF-1's expression across genders and its impact on cardiac function and inflammation. Results indicate a significant gender-specific upregulation of AIF-1 in female murine hearts during septic shock, suggesting a protective role of this molecule in mitigating cardiac dysfunction. In contrast, AIF-1 knockout female mice exhibited exacerbated cardiac dysfunction compared to their wild-type counterparts, as evidenced by decreased ejection fraction and fractional shortening, increased expression of pro-inflammatory cytokines (TNF-α, IL-6), and heightened cardiac inflammation. Moreover, AIF-1 deletion reduced macrophage infiltration in the heart, underscoring its role in modulating immune responses during septic challenges. These findings highlight the protective effects of AIF-1 in female mice and suggest its potential as a therapeutic target for sepsis-induced cardiac dysfunction. Understanding AIF-1's mechanisms may facilitate the development of gender-specific treatments to improve outcomes in sepsis, particularly by leveraging its role in enhancing cardiac resilience and modulating inflammation.