Moreover, healthy female volunteers challenged with either lipopolysaccharide or lipoteichoic acid showed less pro-inflammatory response than males as demonstrated by lower levels of tumor necrosis factor-a, interleukin-1b, IL-6 and IL-8 in blood. In addition, severely injured male traumapatients had a higher incidence of sepsis, multiple organ dysfunction syndrome and greater elevations in plasma procalcitonin and IL-6 compared with the equivalent group of females. Further basic research studies also confirmed these clinical data on gender dimorphism following sepsis. These experimental studies suggested that females had immunologic advantage and showed a significantly increased survival rate compared with males following induction of polymicrobial sepsis by cecal ligation and puncture . In addition, estrogen treatment attenuated the liver dysfunction and intestine injury caused by sepsis in rats with decreased serum aspartate aminotransferase, alanine aminotransferase levels and ameliorated oxidative organ damage, while testosterone receptor blockade with flutamide following trauma-hemorrhage restored immune depression and significantly decreased the mortality after a subsequent septic challenge in male animals. However, little is known about the impact of gender dimorphism on cardiac dysfunction caused by sepsis. Moreover, the mechanisms underlying the gender difference in susceptibility of the heart to a septic challenge are not understood. The present study was designed to determine whether the severity of myocardial dysfunction caused by either co-administration of LPS/peptidoglycan or polymicrobial sepsis induced by CLP differs in male and female mice. Having found that the cardiac dysfunction associated with sepsis was less pronounced in female than in male mice, we have then investigated the potential signalling pathways that may have contributed to the observed differences. We describe here for the first time that the myocardial dysfunction caused by LPS/PepG is less pronounced in female than in male mice in vivo. This finding is in agreement with the previous reports showing that the cardiac dysfunction caused by myocardial ischemia/reperfusion injury, trauma-hemorrhage and burns is also less pronounced in females than in males. Estrogen modulates a number of acute injury-related myocardial responses; specifically estrogen protects the heart against the injury and dysfunction caused by trauma-hemorrhage and ischemia/reperfusion injury . Although we provide clear evidence that female hearts show less dysfunction than male murine hearts when challenged with LPS/PepG, we wished to confirm this finding by using a more clinically relevant model of polymicrobial sepsis with antibiotic therapy and fluid-resuscitation caused by CLP in middle-aged mice . The age of mice was selected based on the knowledge that 8 month-old female C57BL/ 6 mice are pre-ovarian failure and still have an active estrus cycle.