Effect of nonsteroidal anti-inflammatory agents on immune complex- and chemotactic factor-induced inflammation.
Previously we reported that indomethacin and acetylsalicylic acid (ASA) inhibited leukocyte infiltration, blood flow, and vascular permeability during E. coli-induced inflammation in rabbit skin. Here we report the kinetics of these responses and the effects of these drugs on them, when a phagocytic stimulus, such as the immune complexes in the reverse Arthus reaction, or a nonphagocytic stimulus, such as the chemotactic factor in zymosan-activated plasma (ZAP, C5a des Arg), initiate inflammation. Both reactions causes infiltration of 51Cr-labeled leukocytes, an increase in blood flow, measured with 86RbC1, and in vascular permeability, measured with 125I-albumin. In both reactions, all three of these parameters were simultaneously inhibited by indomethacin or ASA. The local injection of prostaglandin E2 (0.5 microgram) at doses which, in control (uninflamed) skin increased only the blood flow, reversed all three inhibitory effects of the drugs. These results indicate that the drug-induced inhibition of leukocyte infiltration was secondary to the inhibition of the vascular responses. Furthermore, the vascular responses in both types of lesions were probably mediated, in large part, by vasodilatory prostaglandins. The magnitude and course of the vascular responses and their sensitivity to the prostaglandin synthetase inhibitors was similar in the Arthus (phagocytic) and in the ZAP (nonphagocytic) lesions. These results suggest that phagocytosis may not be a prerequisite for the generation of prostaglandins and the vascular responses during polymorphonuclear leukocyte-mediated inflammation in vivo.
D000818:Animals; D000936:Antigen-Antibody Complex; D001241:Aspirin / Q000494:pharmacology*; D002630:Chemotactic Factors / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D007213:Indomethacin / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D007700:Kinetics; D010587:Phagocytosis; D011458:Prostaglandins E / Q000494:pharmacology*; D011817:Rabbits
D000936:Antigen-Antibody Complex; D002630:Chemotactic Factors; D011458:Prostaglandins E; D001241:Aspirin; D007213:Indomethacin