Interleukin-6 links psychological trauma and cardiovascular dysfunction

Post-traumatic stress disorder (PTSD) is characterized by debilitating behavioral manifestations, but also by the significantly enhanced probability of developing chronic inflammation and cardiovascular disorders, such as hypertension and stroke. Interleukin 6 (IL-6) is a proinflammatory cytokine that is significantly upregulated in PTSD patients and is heavily implicated in cardiovascular pathologies and vascular dysfunction. Using a murine model of psychological trauma known as repeated social defeat stress (RSDS), we have shown these mice display 10-fold elevated IL-6 levels (p<0.0001) as well as heightened blood pressure sensitivity to angiotensin II (AngII; p<0.05). However, it remains unclear if RSDS-induced IL-6 plays a role in the cardiovascular pathophysiology caused by psychological trauma. Therefore, we hypothesized that IL-6 was directly leading to vascular dysfunction in RSDS animals. We first observed that RSDS led to a 3-fold decrease in plasma nitric oxide (NO) levels (p=0.0360). This decrease in NO bioavailability was further supported by an approximate 10-fold decrease in aortic vascular phosphorylated vasodilator-stimulated phosphoprotein (p-VASP), which is an indicator of NO bioavailability in the vasculature. Mesenteric arteries from RSDS mice also demonstrated decreased acetylcholine and sodium nitroprusside-induced vasodilation, demonstrating the potential for both endothelial dysfunction as well as the ability for the smooth muscle to respond to NO and dilate after RSDS. IL-6 was shown to be causal to the RSDS-induced decreased vascular NO bioavailability as both genetic and pharmacological blockade of IL-6 showed elevated levels of p-VASP after RSDS. Ongoing studies are currently examining RSDS-induced vascular reactivity changes in the absence of IL-6 as well as how IL-6 impacts the potentiated sensitization to AngII after RSDS. Overall, our data suggest IL-6 may be a primary driver of psychological trauma-induced cardiovascular pathology, which provides a novel therapeutic target for patients with PTSD. NIH R01HL158521 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.