Sex Differences in Proatherogenic Cytokine Levels

Abstract

Background: It has been shown that sex affects immunity, including cytokine production. Given that atherosclerosis is an inflammatory disease promoted by specific cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, we aimed at evaluating whether sex could affect the levels of these proatherogenic cytokines in a group of healthy adults. In this analysis, we also included other cytokines and peptides that have been implicated in atherosclerosis development and progression. Methods: A total of 104 healthy adults were recruited; we measured circulating levels of IL-1β, IL-6, TNF-α, angiotensins and angiotensin-converting enzyme-2 (ACE2), as well as osteoprotegerin and receptor activator of nuclear factor κB ligand (RANKL). Results: IL-1β, IL-6, and TNF-α were significantly higher in men as compared to women. They were all associated with testosterone and the testosterone/estradiol ratio. They remained significantly associated with sex (but not with hormones) after being tested for potential confounders. Conclusions: Sex seems to influence the levels of proatherogenic cytokines. This is consistent not only with sex differences in vulnerability to infections but also with the higher cardiovascular risk exhibited by the male gender as compared to the female gender. Nevertheless, this association is only partly explained by hormone levels.

Reproducibility of serum cytokines in an elderly population

“…Results from previous studies demonstrated sex differences in levels of some cytokines among young adults (median age = 22 years) [41], and in cytokine secretion responsiveness of lymphomonocytes under stress conditions [42]. We found nonsignificant differences of cytokine levels (data not shown, p > 0.10) and similar reproducibility of cytokines between older males and females in this study, which might be due to the depletion of sex steroid hormones in elderly subjects.…”

Clinical characteristics and outcomes among Brazilian patients with severe acute respiratory syndrome coronavirus 2 infection: an observational retrospective study

“…20 In addition, the 20 In relation to the body of literature, the mortality rate observed in our study was slightly higher than rates seen in other settings such as China and Italy. [20][21][22][23] Our data suggested that the mortality rate among male Brazilian subjects was higher than the rate among females. This had also been observed in previous studies.…”

“…Initially, it was suggested that women might be less susceptible to viral infections than men due to higher production of circulating antibodies along with prolonged levels of these biomarkers. 22,23 Additionally, another factor that might explain the lower susceptibility of female patients to the novel coronavirus infection is their production of estrogen and immune factors linked to X chromosomes. 24 In women, the double X chromosome affects the immune system with regard to expression of several elements, such as the expression of toll-like receptor 7 (TLR7).…”

Hypothesis: Sex-Related Differences in ACE2 Activity May Contribute to Higher Mortality in Men Versus Women With COVID-19

“…However, a significantly higher ACE2 serum activity was observed in women older than 55 years old compared to women younger than 55 years with no significant difference in serum ACE2 activity between older and younger men. Bernardi et al 21 also found no difference in ACE2 serum level between healthy men and women. In a recently published study in patients with heart failure, defined as left ventricular ejection fraction of ≤40% or plasma concentrations of B-type natriuretic peptide and/or N -terminal pro-brain natriuretic peptide >400 pg/mL or >2000 pg/ml, respectively, serum level of ACE2 was higher in men than in women.…”