Gender Difference in Bacteria Endotoxin-Induced Inflammatory and Anorexic Responses

Abstract

Inflammation-related anorexic response has been observed in systemic diseases as well as in localized infection and is an important issue in patient care. We tested the hypothesis that upon the same endotoxin exposure, males have more severe inflammatory responses and thus suffer from more negative effect on appetite. Ten-week old male and female mice were compared in their plasma levels of pro-inflammatory cytokines after a body weight-based i.p. injection of bacterial endotoxin lipopolysaccharide. Male mice consistently showed significantly higher levels of IL6 and TNFα than female mice. The difference was observed starting at 3 hours after the systemic endotoxin exposure. It was independent of the level of endotoxin dosage and of the genotype of the anti-inflammatory cytokine, IL10. Interestingly, endotoxin-injected male mice also had significantly higher plasma IL10 levels compared to the female mice. Pre-puberty young mice showed no gender differences in the plasma levels of IL6, TNFα and IL10. Their cytokine levels were mostly between that of the adult males and females. Consistent with the higher inflammatory response in male mice, the endotoxin exposure also led to significantly more appetite loss in male mice at a range of doses in two strains of mice. Saline injection in the absence of endotoxin affected neither the cytokine levels nor the appetite. Although a direct mechanistic link between inflammation parameters and appetite was not addressed here, the results support that male gender could be a risk factor for higher pro-inflammatory cytokines and anorexic response after the endotoxin exposure.

Sex Differences in Obesity-Induced Inflammation

“…In contrast Kuo et al used endotoxin exposure in young (5-6 weeks) versus adult (9-10 weeks) male and female mice to investigate relationships in the inflammatory responses in these groups [33]. Older male mice showed significantly higher levels of pro-inflammatory markers IL-6, IL-10, and TNF-alpha than agematched female mice upon stimulation with endotoxin.…”

Sex-differences in LPS-induced neonatal lung injury

“…Given the known influence of sex hormones on the innate immune response 82 , studies have been done examining sex-specific differences in pre- and post-pubertal mice. Following IP LPS challenge, circulating levels of TNFα, IL-6, and IL-10 were not different between pre-pubertal male and female mice 47 . In contrast, post-pubertal mice demonstrated a sex difference, with circulating levels being higher in males compared to females 47 .…”

“…Following IP LPS challenge, circulating levels of TNFα, IL-6, and IL-10 were not different between pre-pubertal male and female mice 47 . In contrast, post-pubertal mice demonstrated a sex difference, with circulating levels being higher in males compared to females 47 . The influence of sex hormones is further highlighted by the finding that pre-pubertal female mice are resistant to LPS-induced mortality comparted to post-pubertal females 104 .…”

“…A number of different factors have been evaluated for sex-specific differences following neonatal hyperoxia exposure, implicated in TLR4-mediated lung injury 26,31,40–46 , or have been demonstrated to have sex-specific differences in LPS-induced expression in adult models 47–49 (Table 3). Furthermore, although LPS injures the developing lung, the liver is central to the innate immune response to endotoxemia 50–64 .…”

Sex‐dependent difference in the relationship between adipose‐tissue cholesterol efflux and estradiol concentrations in young healthy humans

“…Interestingly, the lack of estrogen receptor β (ER‐β) in female mice resulted in increased levels of these cytokines; while no effect was observed in male mice (Wang et al, 2008). Endotoxin exposure has been shown to result in higher levels of pro‐inflammatory cytokine and in anorexic response in male but not in female mice (Kuo, 2016). Temple et al (2008) used endotoxin to stimulate human mononuclear cells, and demonstrated that the expression of TNF‐α and IL10 mRNA were higher in cells obtained from men than women.…”