Endocrine Abstracts

Background: Interleukin (IL)-1 antagonism decreases systolic blood pressure in obese individuals. However, the underlying mechanism is unknown. Based on experimental data in animals we hypothesised a blood-pressure lowering effect of IL-1-antagonism via modulation of the renin-angiotensin-aldosterone system (RAAS).

Methods: In this post-hoc explorative study, we examined short- (2 days) and long-term effects (4 weeks) of IL-1 antagonism (anakinra/Kineret^®) on RAAS-peptide-profiles and on hemodynamic parameters assessed by a non-invasive measurement using HOTMAN^® system. In total, 128 obese (BMI > 30kg/m²) individuals with at least one feature of the metabolic syndrome from two previous interventional trials (CortIL trial a prospective interventional trial (n=61) and TestIL trial, a placebo controlled-double blinded interventional trial (n=67)) were evaluated.

Results: Upon IL-1 antagonism circulating levels of angiotensin II, angiotensin I, aldosterone and renin remained unchanged after short- and long-term treatment, respectively. In contrast, the vasodilatory angiotensin (1–7) peptide significantly increased after 4 weeks compared to placebo (in between group difference 16.35 pmol/L [1.22 to 30.17], P=0.03), without short-term effect on day 2. Concurrently, angiotensin (1–7) /angiotensin II-ratio significantly increased after 4 weeks in the anakinra-group compared to placebo (in between group difference 0.42 pmol/L [0.17 to 0.67], P=0.02). Non-invasive hemodynamic measurement revealed a decrease in the stroke systemic vascular resistance index (SSVRI) with an in between group difference of −62.65 dyn.sec.cm-5.m² [95% CI −116.94 to −18.36], P=0.008 (consistent with a 25%-decrease) after 4 weeks of treatment compared to baseline.

Conclusion: IL-1 antagonism increased the vasodilatory angiotensin (1–7) peptide after 4 weeks of treatment in obese individuals with features of the metabolic syndrome. This was consistent with a decrease in peripheral vascular resistance, reflected by the SSVRI. Thus, these findings point to a possible IL-1 mediated blood pressure lowering mechanism via modulation of the RAAS-System.