Cyclooxygenase-1 Or -2 - Which One Mediates Lipopolysaccharide-Induced Hypothermia?
Systemic inflammation is associated with either fever or hypothermia. Fever, a response to mild systemic inflammation, is mediated by cyclooxygenase (COX)-2 and not by COX-1. However, it is still disputed whether COX-2, COX-1, neither, or both mediate(s) responses to severe systemic inflammation, and, in particular, the hypothermic response. We compared the effects of SC-236 (COX-2 inhibitor) and SC-560 (COX-1 inhibitor) on the deep body temperature (T b) of rats injected with a lower (10 Î¼g/kg iv) or higher (1,000 Î¼g/kg iv) dose of LPS at different ambient temperatures (Tas). At a neutral Ta (30Â°C), the rats responded to LPS with a polyphasic fever (lower dose) or a brief hypothermia followed by fever (higher dose). SC-236 (2.5 mg/kg iv) blocked the fever induced by either LPS dose, whereas SC-560 (5 mg/kg iv) altered neither the febrile response to the lower LPS dose nor the fever component of the response to the higher dose. However, SC-560 blocked the initial hypothermia caused by the higher LPS dose. At a subneutral Ta (22Â°C), the rats responded to LPS with early (70-90 min, nadir) dose-dependent hypothermia. The hypothermic response to either dose was enhanced by SC-236 but blocked by SC-560. The hypothermic response to the higher LPS dose was associated with a fall in arterial blood pressure. This hypotensive response was attenuated by either SC-236 or SC-560. At the onset of LPS-induced hypothermia and hypotension, the functional activity of the COX-1 pathway (COX-1-mediated PGE2 synthesis ex vivo) increased in the spleen but not liver, lung, kidney, or brain. The expression of splenic COX-1 was unaffected by LPS. We conclude that COX-1, but not COX-2, mediates LPS hypothermia, and that both COX isoforms are required for LPS hypotension. Copyright Â© 2009 the American Physiological Society.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology
Digital Object Identifier (DOI)
Steiner, Alexandre A.; Hunter, John C.; Phipps, Sean M.; Nucci, Tatiane B.; Oliveira, Daniela L.; Roberts, Jennifer L.; Scheck, Adrienne C.; Simmons, Daniel L.; and Romanovsky, Andrej A., "Cyclooxygenase-1 Or -2 - Which One Mediates Lipopolysaccharide-Induced Hypothermia?" (2009). Translational Neuroscience. 361.