The circulating cytokine profile in pulmonary arterial hypertension (PAH) is dependent on redox and sex, a new study published in Translational Research found. This could explain the disease’s sexual dimorphism, and it underscores the importance to stratify patients receiving anti-inflammatory therapies.

Inflammatory responses and altered redox homeostasis both occur in a sex-specific manner and are known to play a role in the development of PAH. However, the contribution of sex and oxidative stress to the profile of circulating cytokines has not been investigated.

In the present study, a team of researchers led by Olga Rafikova, MD, PhD, from the University of Arizona College of Medicine in Tucson assessed the impact of sex and plasma redox status on circulating cytokine profiles. The researchers used the oxidation-reduction potential as a measure of redox potential and analyzed it in men and women with group 1 PAH and compared it to healthy controls.

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They compared the profiles of 27 circulating cytokines in the 2 PAH groups having the highest and lowest quartile for plasma oxidation-reduction potential and correlated this with clinical parameters and predict survival.

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They found that there was a correlation between increased cytokine levels and increased oxidative stress in women whereas in men, increased cytokine levels correlated with a lower oxidative environment apart from IL-1b.

“Correlations of the increased cytokine expressions with PAH severity were highly sex-dependent and corresponded to the increase in PAH severity in males and less severe PAH in females,” the researchers wrote. Using machine learning algorithms, they were able to predict PAH mortality with an accuracy of 80%.

PAH is a rare and progressive disease characterized by the narrowing and thickening of the pulmonary arteries. Although the prognosis of the disease has improved over the past years, it remains poor if patients are not diagnosed early and treated in the right way.


Rafikov R, Rischard F, Vasilyev M, et al. Cytokine profiling in pulmonary arterial hypertension: the role of redox homeostasis and sex. Transl Res. Published online April 9, 2022. doi:10.1016/j.trsl.2022.03.013