Thermoregulatory responses to
lipopolysaccharide (LPS) are affected by modulators that increase (propyretic) or decrease (cryogenic) body temperature (Tb). We tested the hypothesis that central
hydrogen sulfide (H2S) acts as a thermoregulatory modulator and that H2S production in the anteroventral preoptic region of the hypothalamus (AVPO) is increased during
hypothermia and decreased during
fever induced by bacterial
lipopolysaccharide (LPS, 2.5mg/kg i.p.) in rats kept at an ambient temperature of 25°C. Deep Tb was recorded before and after pharmacological inhibition of the
enzyme cystathionine β-synthase (CBS - responsible for H2S endogenous production in the brain) combined or not with LPS administration. To further investigate the mechanisms responsible for these thermoregulatory adjustments, we also measured
prostaglandin D2 (
PGD2) production in the AVPO. LPS caused typical
hypothermia followed by
fever. Levels of AVPO H2S were significantly increased during
hypothermia when compared to both euthermic and febrile rats. Intracerebroventricular (icv) microinjection of
aminooxyacetate (AOA, a CBS inhibitor; 100 pmol) neither affected Tb nor basal
PGD2 production during euthermia. In LPS-treated rats, AOA caused increased Tb values during
hypothermia, along with enhanced
PGD2 production. We conclude that the gaseous messenger H2S modulates
hypothermia during endotoxic
shock, acting as a cryogenic molecule.