Plasma Levels of Estradiol and Progesterone are Positively Associated with IL-1α and IL-1Ra in Young Women with PTSD
Authors: Ahmed Zynab , Corbin Chasity , Tahsin Chowdhury Tasnova , Tahmin Chowdhury Ibtida , Waterro Redeat , Mohamed Azhaar , Michopoulos Vasiliki 
Published: May 2024

Introduction: Post-traumatic stress disorder (PTSD) is independently associated with greater cardiovascular disease (CVD) risk. Prior studies have reported higher inflammation as a possible underlying mechanism. Premenopausal females are typically thought to be protected from CVD due to estradiol (E2) and available data supports growing CVD risk in females before menopause by virtue of having PTSD. Given that E2 and progesterone (P4) have been shown to have a broad range of both pro- and anti-inflammatory effects, the purpose of our study was to investigate whether plasma levels of E2 and P4 are associated with subclinical inflammation in young women with PTSD. We hypothesized that E2 and P4 will be negatively associated with IL-1α, IL-1Ra, and IL-6. Methods: Seventy-five otherwise healthy young women (age, 28±7 years; BMI, 26.7±6 kg/m2) with a prior clinical diagnosis of PTSD (PTSD+, n=39) and without a PTSD diagnosis (PTSD-, n=36) were included in this study. We collected blood plasma samples to quantify E2 and P4 and inflammatory biomarkers Interleukin-1α (IL-1α), Interleukin-1 receptor antagonist (IL-1Ra) and Interleukin-6 (IL-6). Total plasma levels of E2 and P4 were measured using the quantitative sandwich enzyme immunoassay technique (ELISA). The inflammatory biomarkers were quantified using a Luminex assay. Participants were also asked to complete a self-administered PTSD checklist for DSM-5 (PCL5) to assess the severity of PTSD symptoms. We ran Pearson correlations between the sex hormones and the inflammatory biomarkers stratified by PTSD diagnosis. Results: We found a positive correlation between E2 levels and IL-1α (r=0.39, p=0.018), E2 and IL-1Ra (r=0.35, p=0.030), P4 and IL-1α (r=0.45, p=0.005), and P4 and IL-1Ra (r=0.27, p=0.101) in the PTSD+ group. In contrast, in the PTSD- group, there was no correlation between E2 and IL-1α (r=0.05, p=0.77), E2 and IL-1Ra (r=-0.06, p=0.73), P4 and IL-1α (r=-0.04, p=0.83) and P4 and IL-1Ra (r=0.07, p=0.68). Conclusion: Our analysis revealed that in young women with a clinical diagnosis of PTSD, E2 and P4 levels in the blood are positively associated with an increased IL-1α and IL-1Ra but not in young trauma-exposed women without PTSD. These findings suggest that in young women with PTSD, E2 and P4 might have a paradoxical effect on inflammation such that E2 and P4 promote the release of both pro-inflammatory (i.e. IL-1α) and anti-inflammatory (i.e. IL-1Ra) cytokines. Conversely, an increase in subclinical inflammation could lead to an increase in E2 and P4 levels, which in turn would promote the release of anti-inflammatory cytokines in order to inhibit the inflammatory response.

K01HL161027 and UMN CTSI UL1TR002494 No Disclosure.

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.