The roles of prostaglandin E2 and D2 in lipopolysaccharide-mediated changes in sleep.

When living organisms become sick as a result of a bacterial infection, a suite of brain-mediated responses occur, including fever, anorexia and sleepiness. Systemic administration of lipopolysaccharide (LPS), a common constituent of bacterial cell walls, increases body temperature and non-rapid eye movement (NREM) sleep in animals and induces the production of pro-inflammatory prostaglandins (PGs). PGE 2 is the principal mediator of fever, and both PGE 2 and PGD 2 regulate sleep–wake behavior. The extent to which PGE 2 and PGD 2 are involved in the effect of LPS on NREM sleep remains to be clarified. Therefore, we examined LPS-induced changes in body temperature and NREM sleep in mice with nervous system-specific knockouts (KO) for the PGE 2 receptors type EP 3 or EP 4 , in mice with total body KO of microsomal PGE synthase-1 or the PGD 2 receptor type DP, and in mice treated with the cyclooxygenase (COX) inhibitor meloxicam. We observed that LPS-induced NREM sleep was slightly attenuated in mice lacking EP 4 receptors in the nervous system, but was not affected in any of the other KO mice or in mice pretreated with the COX inhibitor. These results suggest that the effect of LPS on NREM sleep is partially dependent on PGs and is likely mediated mainly by other pro-inflammatory substances. In addition, our data show that the main effect of LPS on body temperature is hypothermia in the absence of nervous system EP 3 receptors or in the presence of a COX inhibitor. [ABSTRACT FROM AUTHOR]