| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Injection of carrageenan into the hind paw of rats evokes localized inflammation as well as systemic symptoms including fever. However, the mechanism of this inflammation-induced fever is not known. To clarify this mechanism, we analyzed prostagrandin E_2 (PGE_2), which triggers fever, cyclooxygenase-2 (COX-2) and microsomal prostagrandin E synthase (mPGES), both of which are required for PGE_2 biosynthesis, with this experimental model. Fever evoked by carageenan was suppressed by administration of an enzyme inhibitor for COX-2 and was accompanied with a rise in PGE_2 in the cerebrospinal fluid (CSF), and expression of COX-2 in the brain endothelial cells. When measured at 5 time points, i.e., 1.5, 3, 6, 12, f 24 he after carageen an injection, edema, fever, PGE_2 and COX-2-integrated-iritensiry followed a similar time course until 6 hours, at which time all of these measures were at their peaks. After that, fever and PGE_2 returned to the baselines promptly whereas the COX-2-integrated-intensity and edema volume decreased only partially. Unlike these, mPGES integrated-intensity rose more slowly than the above elements to its peak at 12 hr and the level was almost the same at 24 hr. These results imply that expression of COX-2 and mPGES in brain endothelial cells lead to the production of PGE_2 resulting in fever caused by peripheral inflammation and also suggests that, in the recovery phase of fever, there is a recruitment of unidentified mechanism that suppresses PGE_2 formation even in the presence of COX-2 and mPGES. In conclusion, COX-2 and mPGES expression in brain endotherial cells play an essential role in the inflammation-induced fever by producing PGE_2.
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