The findings of this cross-sectional study on PCOS patients demonstrated an inverse association between serum Se and SELENOP levels with pro-inflammatory markers of IL-6, TNF- α, and NF-кB p65. No correlation was observed between serum levels of Se and SELENOP and IL-1β and hs-CRP. This is the first study to evaluate the association of Se and SELENOP levels with markers of systemic inflammation in PCOS patients.
Se is mostly known for its antioxidant activities [18]. However, this element also possesses anti-inflammatory properties [19]. Previous data have shown a negative association between serum Se levels and the inflammatory cytokine of IL-6 in the elderly population in the USA [20] and Taiwan [21]. A study of cirrhosis patients confirmed previous findings, as Se levels were inversely correlated with IL-6 levels [22]. Similarly, in a case-control study, there was a significant indirect relationship between serum Se levels and IL-6 and TNF-α in diabetic patients [23]. Moreover, in an Italian cross-sectional study of 858 healthy controls and 606 patients with cardiovascular disease (CVD), Se deficiency was associated with higher levels of CRP in both healthy and CVD subjects. The investigators also found that gene expression of IL-1β was higher in Se deficient CVD patients compared to the rest of these patients. However, Se deficiency was not associated with gene expression of IL-6, IL-8, and IL-10 in the same study [24].
PCOS is an inflammatory disorder [25] that leads to neutrophil hyperactivity and increased production of ILs, TNF-α, and reactive oxygen species (ROS) in patients with this condition [26]. Abdominal obesity, which is common in PCOS, may play a role in the inflammatory state. However, considering that systematic inflammation has also been reported in non-obese PCOS patients, a genetic basis for the chronic low-grade inflammation observed in PCOS has been proposed [27]. In the present study, we postulated that Se and SELENOP, which accounts for at least 40% of the Se content in human plasma [28], may contribute in the inflammatory state of PCOS. Analysis of data from 125 women with PCOS, showed an inverse association between serum Se and SELENOP levels and inflammatory markers of IL-6, TNF-α, and NF-кB p65. However, we did not find a significant association between serum Se and SELENOP levels and IL-1β and hs-CRP. However, lower Se levels have been reported in PCOS patients [29, 30], but we are not aware of any observational study on the association between Se and markers of inflammation in these patients. However, a few interventional studies have been conducted on the effect of Se supplementation on systemic inflammation in PCOS patients. For example, in a randomized, double-blind, placebo-controlled clinical trial, co-supplementation of probiotics and Se significantly decreased hs-CRP after 12 weeks [31]. Se supplementation reduced hs-CRP levels in another interventional study of 64 women diagnosed with PCOS [13]. Interestingly, however, we did not observe any correlation between Se and CRP levels in this study. This could be due to the small sample size of the current study or the possibility of a more significant effect of Se as a supplement. It should be noted that the assessment of inflammation in the above-mentioned studies was limited to CRP, and the investigators did not use a comprehensive panel of inflammatory biomarkers. In addition, the low power of these studies and the limitations of the interventional study design in generalizing the data make their results unreliable.
Se can inhibit the activation of NF-κB by modulating the expression of selenoprotein genes. The NF-κB pathway contributes to the enhancement of inflammatory response and has been significantly correlated with IL-6 and TNF-α production [32]. The antioxidant activity of Se may result in the reduction of inflammation, as reactive oxygen and nitrogen species (RONS) play a significant role in the modulation of many inflammatory pathways [33]. Se can also downregulate the expression of inflammatory genes [34].
This is the first observational study on the association between serum Se levels and systemic inflammation in women with PCOS. However, the main strength of this study is to evaluate the association between SELENOP, as one of the active agents of Se, and inflammation, rather than focusing only on the contribution of Se. We also examined the association between Se and SELENOP with a wide range of inflammatory markers. However, the limitations of the present study cannot be ignored. Due to the cross-sectional design of our study, we could not determine causality. There is also the effect of unmeasured covariates.