The Number of X Chromosomes Influences Inflammatory Cytokine Production Following Toll-Like Receptor Stimulation

Abstract

Sex differences are observed in the evolution of numerous inflammatory conditions. Women exhibit better clinical courses compared to men in acute inflammatory processes, yet worse prognosis in several chronic inflammatory diseases. Inflammatory markers are significantly different between prepubertal boys and girls, whose sex steroid levels are very low, suggesting genetics play a role. To evaluate the potential influence of the X chromosome, we studied cytokine production and protein phosphorylation following Toll-like receptor (TLR) activation in whole blood and purified neutrophils and monocytes of healthy adults of both sexes as well as subjects with Klinefelter syndrome. We recorded higher levels of inflammatory cytokines in men compared to both women and patients with Klinefelter syndrome following whole blood stimulation. In purified monocytes, production of inflammatory cytokines was also higher in men compared to women, while Klinefelter subjects expressed the same pattern of cytokine production as males, in contrast with whole blood analyses. These differences remained after adjusting for sex steroid levels. Our study revealed higher cytokine inflammatory responses in men than women, yet also compared to subjects with Klinefelter syndrome, who carry two copies of the X chromosome, like women, and thus potentially benefit from the cellular mosaicism of X-linked genes.

Olfactory taste disorder as a presenting symptom of COVID-19: a large single-center Singapore study

“…It was proposed that this difference could have resulted in a higher proportion of female patients having OTD [ 7 ]. However, Lefévre et al [ 23 ] found in their study that there was a higher cytokine inflammatory response in men than women. If gender-related differences in the inflammatory reaction were to be at play, males should be more at risk of OTD, which has not been shown to be the case in multiple studies, including ours.…”

“…This is consistent with other studies [ 5 , 7 , 22 ]. Gender-related differences in the inflammatory reaction process have been well studied [ 23 ]. It was proposed that this difference could have resulted in a higher proportion of female patients having OTD [ 7 ].…”

Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study

“…Moreover, regarding our results, future studies have to explore the potential gender differences in the development of anosmia. The highest susceptibility of females to develop olfactory and gustatory dysfunctions would be related to the gender-related differences in the inflammatory reaction process [23].…”

Hypogeusia as the initial presenting symptom of COVID-19

“…12 The higher susceptibility of women to develop olfactory and subsequent gustatory dysfunction may also be related to sex differences in inflammatory cytokine production. 13 Future studies exploring gender and additional demographic differences in patients with COVID-19 who experience anosmia are warranted.…”