The action mechanism of cyclooxygenase-2 inhibitor for treatment of experimental allergic neuritis.
We previously reported the effect of a cyclooxygenase (COX)-2 inhibitor, nimesulide, on experimental allergic neuritis (EAN) in both the induction and effector phases, in contrast to the usual COX inhibitor, which was effective only when administered in the induction phase. To assess the mechanism of action of a COX-2 inhibitor, we studied the expression of COX-2 and assayed plasma levels of prostaglandins, and also compared the clinical effect of a COX-2 inhibitor with a 5-lipoxygenase (LO) inhibitor, which is responsible for another pathway of arachidonic acid metabolism. Nerves of EAN rats showed distinct expression of COX-2, which is derived mostly from endoneurial macrophages. Treatment with a COX-2 inhibitor had no effect on its expression. However, prostaglandin estradiol (E(2)) concentration of plasma was significantly lower compared with the control group. The LO inhibitor showed no clinical effect. These results suggest that a selective COX-2 inhibitor is effective in the effector phase by its influence on macrophages that are responsible for nerve degeneration.
Miyamoto
K
K
Department of Neurology, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan.
Oka
N
N
Kawasaki
T
T
Satoi
H
H
Matsuo
A
A
Akiguchi
I
I
D000818:Animals; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000097:blood; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use; D008297:Male; D009068:Movement / Q000502:physiology; D009412:Nerve Fibers / Q000473:pathology; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000473:pathology; D020426:Sciatic Neuropathy / Q000473:pathology; D013449:Sulfonamides / Q000627:therapeutic use
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C012655:nimesulide