Gao W, Schmidtko A, Wobst I, Lu R, Angioni C, Geisslinger G
Pharmazentrum Frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
J Physiol Pharmacol. 2009 Jun;60(2):145-50.
A large body of evidence has implicated prostaglandin E(2) (PGE(2)) in fever production. However, the role of PGD(2) in this context is only poorly understood. We therefore determined by LC-MS/MS analyses the content of PGD(2) and PGE(2) in cerebrospinal fluid (CSF), plasma and lungs of rats over 5 hours after fever induction by intraperitoneal injection of lipopolysaccharide (LPS, 50 microg/kg). Both PGD(2) and PGE(2) were detected in CSF, plasma and lungs of saline-treated control animals. The injection of LPS evoked fever and an increase of PGE(2) in the CSF, while the CSF content of PGD(2) was not significantly altered. However, both PGE(2) and PGD(2) levels were elevated in plasma and lungs after LPS injection. Interestingly, pretreatment with a novel selective inhibitor of hematopoietic prostaglandin D synthase (H-PGDS), EDJ300520 (10-40 mg/kg p.o.), selectively and dose-dependently prevented the LPS-induced increase of PGD(2) in plasma and lungs but did not affect the PGE(2) content. Most remarkably, EDJ300520 pretreatment led to an hypothermic response after LPS injection during the first 3 h and prevented fever induction. These data indicate that PGD(2) produced peripherally by H-PGDS essentially contributes to LPS-induced fever.
大量证据表明前列腺素E(2)（PGE(2)）与发热产生有关。然而，在此背景下PGD(2)的作用却知之甚少。因此，我们通过液相色谱-串联质谱分析（LC-MS/MS）测定了腹腔注射脂多糖（LPS，50微克/千克）诱导发热后5小时内大鼠脑脊液（CSF）、血浆和肺中PGD(2)和PGE(2)的含量。生理盐水处理的对照动物的脑脊液、血浆和肺中均检测到了PGD(2)和PGE(2)。注射LPS可引起发热并使脑脊液中PGE(2)增加，而脑脊液中PGD(2)的含量无显著变化。然而，注射LPS后血浆和肺中PGE(2)和PGD(2)水平均升高。有趣的是，用新型造血前列腺素D合酶（H-PGDS）选择性抑制剂EDJ300520（10-40毫克/千克口服）预处理，可选择性且剂量依赖性地阻止LPS诱导的血浆和肺中PGD(2)的增加，但不影响PGE(2)含量。最显著的是，EDJ300520预处理在注射LPS后的前3小时导致体温过低反应，并阻止了发热诱导。这些数据表明，由H-PGDS在周围产生的PGD(2)在很大程度上促成了LPS诱导的发热。
