抄録
Prostaglandin E2 (PGE2), the final mediator of fever, is thought to be produced in brain endothelial cells through the enzyme cascade of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1), since various pyrogenic stimuli induce these enzymes in brain endothelial cells. The essential role of COX-2 in brain PGE2 synthesis and fever has been shown by using COX-2-specific inhibitors or COX-2-gene deficient mice. We here examined the role of mPGES-1 in these reactions by using mPGES-1 gene deficient (mPGES-1(-/-)) mice. Abdominal temperature of mPGES-1(-/-) mice and wild type mice were monitored with a telemetry system. The mice were challenged with 4 pyrogenic stimuli, i.e., lipopolysachharide (LPS, intraperitoneal injection), turpentine (subcutaneous injection), interleukin-1 beta (intracerebroventricular injection), and PGE2 (intracerebroventricular injection). Both types of mice responded to PGE2 with a similar degree of fever, whereas pyrogenic stimuli other than PGE2 evoked fever only in wild type mice. The LPS stimuli elevated PGE2 level in the brain only in wild type mice whereas LPS-induced plasma interleukin-1 beta and brain endothelial COX-2 levels were similar in these two types of mice. These results clearly demonstrate that mPGES-1 plays an essential role in the brain PGE2 synthesis and fever under various inflammatory/infectious states. [Jpn J Physiol 54 Suppl:S230 (2004)]
