Role of the preoptic carbon monoxide pathway in endotoxin fever in rats

Recently, we have reported that the heme oxygenase (HO)-carbon monoxide (CO) pathway plays an important role in the genesis of LPS fever, acting through a cGMP signaling pathway in the brain, but the site of action remains unclear. Thus, the present study was designed to test the hypothesis that the HO-CO pathway mediates fever by acting on the preoptic region of the anterior hypothalamus (POA), which is the brain body core temperature (T(c)) controller site. To this end, the T(c) of rats was monitored by biotelemetry before and after pharmacological modulation of the HO-CO pathway. It was observed that intra-POA administration of the HO inhibitor ZnDPBG (5 nmol) produced no thermoregulatory effect and did not affect LPS (100 microg/kg, i.p.) fever compared to the group treated with the ZnDPBG vehicle, indicating that the HO-CO pathway in the POA is not involved in fever. In agreement, intra-POA heme-lysinate (3.8 or 7.6 nmol), which is known to induce the HO-CO pathway, evoked no change in T(c) compared to the vehicle-treated group. In summary, the present results support the idea that the POA is not the brain site where the HO-CO pathway acts as a fever mediator.