Sex Differences in Systemic Inflammatory Response in Low Hypoxia-Resistant Rats

Abstract

OBSERVATION. Individual differences in hypoxia tolerance and expression of the hypoxia-inducible factor, HIF-1α, were found in humans and laboratory animals. This allowed us to distinguish groups of animals with low and high resistance to oxygen deficiency. It was shown that low hypoxia-resistant animals are characterized by a more severe course of the systemic inflammatory response (SIR). Sex differences in the severity of SIRS in animals with low hypoxia tolerance have not been studied. OBJECTIVE To characterize morphological and molecular-biological features of lipopolysaccharide (LPS)-induced SIR in low hypoxia-resistant male and female Wistar rats. MATERIALS AND METHODS. Low hypoxia-resistant animals were distinguished by the time of “life” in a hypobaric barocamera at an altitude of 11500 m (less than 60 s). SWO was modeled by intraperitoneal injection of LPS at a dose of 1.5 mg/kg. One day later, morphologic changes in the lungs, liver, and thymus, as well as endotoxin levels, corticosterone, HIF1-α, and TGFβ concentrations in serum from low hypoxia-resistant female and male Wistar rats were evaluated. RESULTS. Differences were found in control groups in females and males of low hypoxia-resistant rats, characterized by higher HIF1-α, corticosterone and endotoxin levels in serum in females. Thus, in females 24 h after LPS injection the number of neutrophils in interalveolar septa of lungs was higher and acute accidental involution of thymus with narrowing of subcapsular zone without changes in volumetric fraction of cortical substance developed. Whereas in males widespread pathological changes in the liver and more pronounced manifestations of accidental involution accompanied by narrowing of the volume fraction of the thymus cortical substance were revealed. In the blood serum of females with SWO, the content of corticosterone increased, while in males the concentration of HIF1-α and the level of endotoxin increased, and the content of TGFβ decreased. CONCLUSIONS. Although female and male rats were characterized by low resistance to hypoxia, the course of LPS-induced SWO and the development of immune reactions in animals have sex differences.