Interleukin-6 contributes to hepcidin mRNA increase in response to exercise

The iron regulatory peptide hormone hepcidin has been proposed to participate in training-induced iron deficiency. Plasma and urinary hepcidin increase in response to one bout of prolonged exercise, a condition also known to increase plasma interleukin-6 (Il-6). Because Il-6 activates hepcidin transcription and expression during inflammation, our aim was to study the role of this cytokine in hepatic hepcidin mRNA expression during exercise and recovery. We used a rodent model of exhaustive running exercise, where rats were treated or not with cyclosporin A (CsA), a calcineurin inhibitor shown to blunt plasma Il-6 during exercise. Despite similar running intensity and duration, animals treated with CsA had 50% lower plasma Il-6 concentrations at the end of exercise. The concomitant rise in hepatic mRNA levels of two Il-6 responsive genes, suppressor of cytokine signaling (SOCS) 3 and Il-6 receptor alpha, was blunted in CsA-treated group. Finally, hepcidin mRNA levels increased in response to exercise, peaking 2 h later, but peak values were significantly lower in CsA group compared to control group. This result strongly suggests that plasma Il-6 is involved in exercise-induced increase of hepcidin gene expression. (C) 2012 Elsevier Ltd. All rights reserved.