Endocrine Abstracts

Background: The goal of this project was to identify non-osmotic stimuli of arginine vasopressin (AVP) release during exercise. Non-osmotic AVP release can lead to severe hyponatremia in otherwise healthy marathon runners.Interleukin-1 (IL-1) increases during exercise and was shown to induce AVP in animal models. We here therefore investigated whether copeptin (a surrogate marker for AVP) increases upon exercise in young and healthy males, and whether this increase is regulated by IL-1. The effect of the IL-1 receptor antagonist anakinra on exercise-induced copeptin was assessed.

Methods: Data from a randomized, placebo-controlled, double-blind crossover trial were analyzed where 17 healthy male volunteers exercised for one hour at 75% of VO_2max and were not allowed to drink/eat 6 hours before and during the study. Participants received either 100 mg of anakinra or placebo one hour before exercise. Blood was drawn at certain time intervals before, during, and after exercise. Statistical analysis: To test for change in copeptin levels over time and for differences between the placebo and the anakinra group, linear mixed-effects models were fit. Fixed-effect explanatory variables were time of measurement (0, 60, 120 min), treatment allocation, and sodium levels. Furthermore, differences in the area under the curve (AUC) for the anakinra and placebo group were analyzed using a Wilcoxon signed rank test.

Findings: In both groups, copeptin levels were induced by 2.5-fold upon exercise (P<0.001), from 4.5–10.6 pmol/l in the placebo, and 4.3–11.3 pmol/l in the anakinra group, with no difference between the groups (P=0.4). One hour after exercise, copeptin levels dropped to 7.7 and 7.9 pmol/l in the placebo and anakinra group, respectively (P=0.6). The increase of copeptin levels was not explained by sodium concentrations (P=0.1). The AUCs of copeptin values for the time during and after exercise were not significantly different when participants were treated either with placebo or anakinra (P=0.7).

Interpretation: Exercise induces a continuous rise of plasma copeptin levels in healthy male volunteers independently of sodium levels and fluid intake. This increase is not regulated by the IL-1 pathway.