Role of corticosterone in modulation of eicosanoid biosynthesis and antiinflammatory activity by 5-lipoxygenase (5-LO) and cyclooxygenase (CO) inhibitors.
The effectiveness of 5-lipoxygenase (LO) and dual LO/cyclooxygenase (CO) inhibitors when administered by the topical or oral routes was significantly decreased in corticosterone depleted (adrenalectomized, Adx) mice as compared to sham mice in the mouse arachidonic acid (AA) induced ear edema model. In contrast, rat carrageenan paw edema was inhibited similarly in sham and Adx animals by 5-LO and dual 5-LO/CO inhibitors. Supplementation of cortisol levels (100 micrograms/dl) in human whole blood for 2 hr increased the observed inhibition of LTB4 biosynthesis by A-64077, WY-50,295 tromethamine and naproxen while having no effect on thromboxane B2 (TXB2) biosynthesis. Thus, corticosteroids may have a permissive effect by modulating 5-LO inhibitor effects on mouse AA induced ear edema and human blood leukocytes.
Tomchek
L A
LA
Wyeth-Ayerst Research, Princeton, NJ 08543-8000.
Hartman
D A
DA
Lewin
A C
AC
Calhoun
W
W
Chau
T T
TT
Carlson
R P
RP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003345:Corticosterone / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004487:Edema / Q000188:drug therapy; D015777:Eicosanoids / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D051381:Rats; D013929:Thromboxane B2 / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4; D013929:Thromboxane B2; D003345:Corticosterone