Suppression of inflammatory oedema by ibuprofen involving a mechanism independent of cyclo-oxygenase inhibition.
The effects of a non-steroidal anti-inflammatory compound, ibuprofen, on experimentally-induced local oedema responses in rabbit skin were investigated. The accumulation of intravenously-injected 125I-albumin was used to measure oedema. Two peptides were used to increase microvascular permeability: C5a des Arg, whose action is dependent on circulating polymorphonuclear leukocytes, and bradykinin which acts directly on vascular endothelial cells. The peptides were injected intradermally together with either arachidonic acid or PGE2 to potentiate oedema formation. To study the cyclooxygenase inhibitory activity of ibuprofen, the effects of the mediators were potentiated by addition of arachidonic acid. To investigate whether the drug had effects independent of cyclo-oxygenase inhibition, PGE2 was used to potentiate responses. Both local and intravenous ibuprofen suppressed oedema induced by bradykinin + arachidonic acid and C5a des Arg + arachidonic acid, which is consistent with suppression of cyclo-oxygenase in the skin. Local ibuprofen had no effect on responses to bradykinin + PGE2 or C5a des Arg + PGE2. Intravenous ibuprofen had no significant effect on responses to bradykinin + PGE2 but, in contrast, had a marked inhibitory effect on responses to C5a des Arg + PGE2. It is concluded that, in addition to its known cyclo-oxygenase inhibitory activity, ibuprofen can inhibit inflammatory oedema at clinically-relevant doses by an action on circulating poly-morphonuclear leukocytes. These observations in vivo appear to be related to other observations on the effects of ibuprofen on polymorphonuclear leukocyte function in vitro and ex vivo. The observations described may also relate to the protective effects of ibuprofen on experimentally-induced myocardial infarction.
Rampart
M
M
Williams
T J
TJ
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D004487:Edema / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D007052:Ibuprofen / Q000008:administration & dosage / Q000627:therapeutic use*; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D007271:Injections, Intradermal; D008297:Male; D011453:Prostaglandins / Q000502:physiology; D011817:Rabbits; D012867:Skin / Q000201:enzymology / Q000503:physiopathology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D011453:Prostaglandins; C039242:dazmegrel; D013930:Thromboxane-A Synthase; D007052:Ibuprofen; D007213:Indomethacin