Two murine models of sepsis: immunopathological differences between the sexes-possible role of TGF1 in female resistance to endotoxemia

Endotoxic shock (ExSh) and cecal ligature and puncture (CLP) are models that induce sepsis. In this work, we investigated early immunologic and histopathologic changes induced by ExSh or CLP models in female and male mice. Remarkable results showed that females supported twice the LD100 of LPS for males, CLP survival and CFU counts were similar between genders, high circulating LPS levels in ExSh mice and low levels of IgM anti-LPS in males. In the serum of ExSh males, TNF and IL-6 increased in the first 6 h, in CLP males at 12 h. In the liver of ExSh mice, TNF increased at 1.5 and 12 h, IL-1 at 6 h. TGF beta 1 increased in females throughout the study and at 12 h in males. In CLP mice, IL-6 decreased at 12 h, TGF beta 1 increased at 6-12 h in males and at 12 h in females. In the lungs of ExSh males, IL-1 beta increased at 1.5-6 h and TGF beta 1 at 12 h; in females, TNF decrease at 6 h and TGF beta 1 increased from 6 h; in CLP females, TNF and IL-1 beta decreased at 12 h and 1.5 h, respectively, and TGF beta 1 increased from 6 h; in males, TGF beta 1 increased at 12 h. In the livers of ExSh mice, signs of inflammation were more common in males; in the CLP groups, inflammation was similar but less pronounced. ExSh females had leucocytes with TGF beta 1. The lungs of ExSh males showed patches of hyaline membranes and some areas of inflammatory cells, similar but fewer and smaller lesions were seen in male mice with CLP. In ExSh females, injuries were less extent than in males, similar pulmonary lesions were seen in female mice with CLP. ExSh males had lower levels of TGF beta 1 than females, and even lower levels were seen in CLP males. We conclude that the ExSh was the most lethal model in males, associated with high levels of free LPS, low IgM anti-LPS, exacerbated inflammation and target organ injury, while females showed early TGF beta 1 production in the lungs and less tissue damage. We didn't see any differences between CLP mice.