Sex differences in systemic inflammatory response in hypoxia-resistant Wistar rats

BACKGROUND: Individual differences in hypoxia tolerance and hypoxia-inducible factor 1 alpha (HIF-1α) expression were identified in humans and laboratory animals. This was the basis for identifying groups of animals with low and high hypoxia tolerance. Animals with low hypoxia tolerance are known to have a more severe course of systemic inflammatory response (SIR). Sex differences in the severity of SIR in low hypoxia-tolerant animals have not been studied. AIM: The aim was to evaluate sex differences in the severity of lipopolysaccharide (LPS)-induced SIR in Wistar rats with low hypoxia tolerance. MATERIALS AND METHODS: Low hypoxia-tolerant animals were determined by their survival time in a hypobaric chamber under conditions equivalent to 11,500 m altitude (less than 60 s). The SIR was modeled by intraperitoneal administration of LPS at 1.5 mg/kg. Morphological changes in the lungs, liver, and thymus, as well as serum levels of endotoxin, corticosterone, HIF-1α, and TGF-β, were evaluated in males and females after 24 hours. RESULTS: In control groups of low hypoxia tolerant rats, higher serum levels of HIF-1α, corticosterone and endotoxin were found in females compared to males. Compared to females, males usually have a higher thymic cortical volume fraction and lower subcapsular thickness. When LPS was administered to low hypoxia-tolerant females and males, sex differences in the severity of SIR were revealed. For example, in females, 24 hours after LPS administration, the neutrophil count in pulmonary interalveolar septa was higher, and random thymic involution with subcapsular zone narrowing developed without changing cortical volume fraction. Males demonstrated large abnormal lesions in the liver and more significant manifestations of accidental involution with a decrease in thymic cortical volume fraction. Serum corticosterone levels increased in females with SIR, and HIF-1α and endotoxin levels increased and TGF-β levels decreased in males. CONCLUSION: LPS-induced SIR and immune responses in low hypoxia-tolerant Wistar rats depend on sex.