| Research Abstract |
We in vestigated the signal tran smission mechanism from the immune system to the nervous system focusing on prostaglandins (PGs). In the early phase of the inflammation, PGs synthesized by macrophases or monocytes at the inflammatory saite, is involved in the inflammatory hyperalgesia by sen sitizing the sensory nerve terminals. The prophylactic administration of selective inhibitor of cyclooxygenase-2 (OOX-2), rate limiting enzyme of PG synthesis, at the inflammatory site was effective in preventing hyperalgesia. Then, in the intermediate to later phase of the inflammation, we got the following results 1) the concentration of PGE_2 in the cerebrospinal fluid (CSF) in creased significantly 2) systemic administration of OOX-2 inhibitor in the intermediate phase, not before the inflammatory on set, suppressed both inflammatory hyperalgesia and the increase in PGE_2 in the CSF 3) intrathecal injection of OOX-2 inhibitor alleviated hyperalgesia even at a small dose 4) degree of hyperalges
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ia, OOX-2 expression and the concentration of PGE_2 in the CSF correlated very well. Furthermore, PGE_2 synthesizing cell in the central nervous system (CNS) was identified; 1) PGE_2 synthesizing enzyme (PGES), the vascular endothelial cells in the CNS 2) OOK-2 and PGES colocalized in the vascular endothelial cell and the percentage of colocalization was more than 90% 3) these OOK-2- and PGES- expressing endothelial cells widely distributed in the brain and the spinal cord without regional differences. These observations are contradictory to the conventional theory that OOX-2 expression are contradictory to the conventional theory that OOX-2 expression and PGE_2 synthesis occur in the neurons. Our systemic symptoms accompanied by peripheral inflammation such as fever up, general fatigue, hyperalgesia. Furthermore, we have got the novel theory of systemic symptoms would be the potent clue to clarify the pathogenesis of systemic symptons accompanied by the potent clue to clarify the pathogenesis of systemic symptoms accompanied by peripheral inflammation such as fever up, general fatigue, signal transmission from theinflammatory site to the CNS based on the fact that vascular endothelial cells synthesize PGE_2 once cytokines bind to cytokine receptors on them; proinflammatory cytokines produced at the peripheral site is involved in the signal transmission to vascular endothelial cells humoraly. We got the preliminary result concerning tcytokines involved in the signal transmission and further investigation is needed for the complete clarification of the mechanism Less
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