Effect of Physical Exercise on the Febrigenic Signaling is Modulated by Preoptic Hydrogen Sulfide Production

We tested the hypothesis that the neuromodulator hydrogen sulfide (H 2 S) in the preoptic area (POA) of the hypothalamus modulates the febrigenic signaling differently in sedentary and trained rats. Besides H 2 S production rate and protein expressions of H 2 S-related synthases cystathionine β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MPST) and cystathionine γ-lyase (CSE) in the POA, we also measured deep body temperature (Tb), circulating plasma levels of cytokines and corticosterone in an animal model of systemic inflammation. Rats run on a treadmill before receiving an intraperitoneal injection of lipopolysaccharide (LPS, 100 μg/kg) or saline. The magnitude of changes of Tb during the LPS-induced fever was found to be similar between sedentary and trained rats. In sedentary rats, H 2 S production was not affected by LPS. Conversely, in trained rats LPS caused a sharp increase in H 2 S production rate that was accompanied by an increased CBS expression profile, whereas 3-MPST and CSE expressions were kept relatively constant. Sedentary rats showed a significant LPS-induced release of cytokines (IL-1β, IL-6, and TNF-α) which was virtually abolished in the trained animals. Correlation between POA H 2 S and IL-6 as well as TNF-α was observed. Corticosterone levels were augmented after LPS injection in both groups. We found correlations between H 2 S and corticosterone, and corticosterone and IL-1β. These data are consistent with the notion that the responses to systemic inflammation are tightly regulated through adjustments in POA H 2 S production which may play an anti-inflammatory role downmodulating plasma cytokines levels and upregulating corticosterone release.