Sex differences of inflammatory and immune response in pups of Wistar rats with SIRS

Abstract

It is a common fact, that the content of sex hormones in humans and animals varies in different age periods. The functional state of the immune system also changes with age. However, sex differences studies of inflammatory and immune responses during puberty prevail in literature. Investigation of immune responses to LPS peculiarities in prepubertal females and males may contribute to the development of more effective immunotherapy and minimize side effects of children vaccination. Therefore, the aim of this work was to investigate the LPS-induced SIRS sex differences in prepubertal Wistar rats. Despite the absence of sex differences in estradiol and testosterone levels, LPS-induced inflammatory changes in liver and lungs are more pronounced among males. Males demonstrate the increasing neopterin, corticosterone levels and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity. Not less important is that in females, demonstrating less morphological changes in liver and lungs, endotoxin level is tenfold higher, and corticosterone level decreases. Thus, endotoxin cannot be used as a marker of the severity of multiple organ failure in prepubertal period. The LPS-induced immune reactions in females and males are similar and are characterized by immunosuppression. Both females and males have decreased production of cytokines (IL-2, IL-4, TNF-α, TGF-β) and the absolute number of CD3 + and CD3 + CD8 + lymphocytes in blood. The acute atrophy of thymus and apoptosis of thymic cells are revealed in animals of both sexes. However, the number of CD3 + CD4 + T-helpers and CD4 + CD25 + Foxp3 + T-cells decreases only in females with SIRS, and in males there was a decrease of CD45R + B-cells. The least expressed sex differences in immune responses in the prepubertal period can be determined by the low levels of sex steroids and the absence of their immunomodulatory effect. Further studies require the identification of mechanisms, determining the sex differences in the inflammatory and immune responses in prepubertal animals.

Fecal microbiota transplantation from HUC-MSC-treated mice alleviates acute lung injury in mice through anti-inflammation and gut microbiota modulation

“…The composition of GM can also influence the development of ALI (Kosyreva et al, 2020 ). By alerting the composition and metabolisms of GM and modulating the balance between beneficial and harmful bacteria, the injured lung can be alleviated and lung immunity can be enhanced (Liu et al, 2020a ).…”

Aberrant Mitochondrial Dynamics and Exacerbated Response to Neuroinflammation in a Novel Mouse Model of CMT2A

“…Given previously published findings reporting a neuroprotective and anti-inflammatory role of MFN2 [ 26 ], Mfn2 +/K357T mice were additionally challenged with LPS in an effort to unmask CMT2A-relevant changes after exposure to a systemic inflammatory stimulus. Due to sex differences in immune responses after LPS-induced systemic inflammation—as male mice are more susceptible to sickness behavior [ 31 , 32 ], display a higher inflammatory response (i.e., IL-6, TNF-α) [ 32 ], and experience more severe LPS-induced tissue pathological changes [ 33 ]—only 6-mo-old male Mfn2 +/+ and Mfn2 +/K357T mice were subjected to LPS treatment. A longitudinal study was conducted using the same mice groups for all LPS experiments, and mice were tested prior to LPS injection (0 h) and up to 96 h after LPS injection.…”

Age-related differences in hypoxia-associated genes and cytokine profile in male Wistar rats

“…Low tolerance to hypoxia and the presence of additional regulation of HIF-1α degradation mechanisms in prepubertal rats may determine their high predisposition to the development of SIRS (Kosyreva et al, 2020). It is known that the development of LPS-induced pro-inflammatory reactions occurs through the activation of NF-κB.…”

“…Possibly, corticosterone plays a significant role in these processes as it is known that the excessive exposure to sustained elevated levels of stress hormones, including corticosterone, can be harmful and predispose to reproductive, immune, metabolic, and cardiovascular disorders (McEwen, 1998). In adult rats, despite the increased level of oxidative stress and production of pro-inflammatory cytokines, tolerance to hypoxia was higher, and SIRS severity was also less than in prepubertal animals (Kosyreva et al, 2019(Kosyreva et al, , 2020.…”

“…Adult animals are divided into tolerant and susceptible to hypoxia according to gasping time assessment in the decompression chamber. Tolerance to hypoxia performs a significant part in the inflammation development (Dzhalilova et al, 2019a,b), since any disturbances of the reactions to a lack of oxygen molecular mechanisms lead to pathological processes that contribute to many inflammatory diseases development (Watts, Walmsley, 2019) It was demonstrated that prepubertal animals have more pronounced SIRS (systemic inflammatory response syndrome) in comparison to adults (Kosyreva et al, 2020). The key pathogenesis factors of SIRS are circulatory disorders and hypoxia.…”