Sex and inflammation in respiratory diseases: a clinical viewpoint

Abstract

This review discusses sex differences in the prognosis of acute or chronic inflammatory diseases. The consequences of severe inflammation vary in relation to sex, depending on illness duration. In the majority of acute diseases, males present higher mortality rates, whereas continuous chronic inflammation associated with tissue damage is more deleterious in females. The recruitment of cells, along with its clinical expression, is more significant in females, as reflected by higher inflammatory markers. Given that estrogens or androgens are known to modulate inflammation, their different levels in males and females cannot account for the sexual dimorphism observed in humans and animals from birth to death with regard to inflammation. Numerous studies evaluated receptors, cytokine production, and clinical outcomes in both animals and humans, revealing that estrogens clearly modulate the immune response, but the results are contradictory and difficult to link to hormone concentrations. Even in prepubescent children, the presentation of acute pneumonia or chronic diseases mimics the adult pattern. Several genes located on the X chromosome have been shown to encode molecules involved in inflammation. Moreover, 10% to 15% of the genes from silenced X chromosome may escape inhibition. Females are also a mosaic of cells with genes from either paternal or maternal X chromosome. Therefore, polymorphism of X-linked genes would result in the presence of two cell populations with distinct regulatory arsenals, providing females with greater diversity to fight against infectious challenges, in comparison with the uniform cell populations in hemizygous males. The similarities observed between males and Turner syndrome patients using an endotoxin stimulation model support the difference in gene expression between monosomy and disomy for the X chromosome. Considering the enhanced inflammation in females, cytokine production may be assumed to be higher in females than males. Even if all results are not clear-cut, nonetheless, many studies have reported higher cytokine levels in both male humans and animals than in females. High IL-6 levels in males correlated with poorer prognosis and shorter longevity. A sound understanding of the basic regulatory mechanisms responsible for these gender differences may lead to new therapeutic targets.

Susceptibility to Lower Respiratory Infections in Childhood is Associated with Perturbation of the Cytokine Response to Pathogenic Airway Bacteria

“…The PCA is described in details in the Supplemental Digital Content 1, http://links.lww.com/INF/C406. All associations were adjusted for gender [21][22][23] and season of birth. [23][24][25] All statistical analysis are based on a linear quasipoison regression, while in the graphical presentation of the results, the children are partitioned into 3 groups based on the number of LRI.…”

Association between serum soluble tumor necrosis factor-α receptors and early childhood obesity

“…However, the estradiol level in girls is apparently higher than the testosterone level in boys among children aged 3-4 years [33]. Estrogens may exhibit diverse effects on inflammation and immune response [32]. The results of the present study suggest that obese girls may be more sensitive to obesityrelated inflammatory response than obese boys.…”

“…Some previous studies have explored the sexual differences of circulating sTNFRs with human obesity [17,28,29]. In addition, other inflammatory markers, such as IL-10, TNF-α, IL-6, IL-8, and CRP, exhibit sexual dimorphism [30][31][32]. The mechanisms underlying these sexual dimorphisms may be multifactorial, such as the release of different hormones.…”

Demographic and mortality analysis of hospitalized children at a referral hospital in Addis Ababa, Ethiopia

“…Additionally, several studies report no relationship between sex and immunization rates in Ethiopia [32][33][34]. There are some limited data which suggest that respiratory illness may be more severe and diarrhea may be more prevalent in males in Ethiopia [35], but these studies primarily included neonates, a cohort not examined in this study. While we are unable to identify why there is such a marked sex disparity in pediatric hospital admissions to ZMH, it is clear that it exists and further investigation regarding social factors that influence care-seeking behaviors and early interventions are warranted.…”