Bilbo S D, Quan N, Prendergast B J, Bowers S L, Nelson R J
Department of Psychology, The Ohio State University, Columbus, OH 43210, USA.
J Neuroendocrinol. 2003 Oct;15(10):958-64. doi: 10.1046/j.1365-2826.2003.01084.x.
Fever is initiated by activation of the arachidonic acid cascade and the biosynthesis of prostaglandins within the brain. Inducible cyclooxygenase (COX-2) is a rate-limiting enzyme in prostaglandin synthesis, and the number of blood vessels expressing COX-2 correlates with elevated body temperature following peripheral lipopolysaccharide (LPS). Despite its importance in host defense, fever is energetically expensive and we hypothesized that fever may be limited by available metabolic resources. During winter, when competing metabolic demands are constrained by low temperatures and food availability, it was predicted that fever duration would be reduced in seasonally breeding Siberian hamsters (Phodopus sungorus). We measured LPS-induced COX-2 expression in blood vessels of hamsters to test whether photoperiodic alterations in fever duration are centrally mediated, or whether they reflect changes in peripheral modulation of body temperature. Hamsters housed in long, 'summer-like' or short, 'winter-like' day lengths for 10 weeks were injected with LPS, and brains were collected 2, 4, or 8 h later. COX-2 expression was comparably increased in long- and short-day hamsters by 2 h and 4 h post-LPS; however, short-day hamsters exhibited significantly fewer COX-2-positive cells and blood vessels by 8 h post-LPS compared to long-day hamsters, corresponding with reduced fever duration in short-day hamsters. Cortisol concentrations increased more than two-fold in short-day compared to long-day hamsters by 4 h; this increase may have contributed to the decrease in COX-2 expression observed by 8 h in short days. We conclude that short photoperiods significantly altered the time course of central COX-2 protein expression in hamsters in a manner consistent with reduced fever duration.
发热是由花生四烯酸级联反应的激活以及大脑中前列腺素的生物合成引发的。诱导型环氧化酶（COX-2）是前列腺素合成中的限速酶，表达COX-2的血管数量与外周脂多糖（LPS）刺激后体温升高相关。尽管发热在宿主防御中很重要，但它在能量方面代价高昂，我们推测发热可能受到可用代谢资源的限制。在冬季，当竞争的代谢需求因低温和食物供应而受到限制时，预计季节性繁殖的西伯利亚仓鼠（Phodopus sungorus）的发热持续时间会缩短。我们测量了仓鼠血管中LPS诱导的COX-2表达，以测试发热持续时间的光周期变化是由中枢介导的，还是反映了体温外周调节的变化。将仓鼠置于长日照（“夏季样”）或短日照（“冬季样”）环境中10周后注射LPS，并在2、4或8小时后收集大脑。LPS注射后2小时和4小时，长日照和短日照仓鼠的COX-2表达均有类似增加；然而，与长日照仓鼠相比，LPS注射后8小时，短日照仓鼠的COX-2阳性细胞和血管明显减少，这与短日照仓鼠发热持续时间缩短相一致。与长日照仓鼠相比，短日照仓鼠在注射LPS后4小时皮质醇浓度增加了两倍多；这种增加可能导致了短日照环境下8小时时观察到的COX-2表达下降。我们得出结论，短光周期显著改变了仓鼠中枢COX-2蛋白表达的时间进程，其方式与发热持续时间缩短一致。
