Effect on the human complement system of the major non-steroidal anti-inflammatory drugs: aspirin, indomethacin, phenylbutazone, oxyphenbutazone and sulindac.
The possibility that the major non-steroidal anti-inflammatory drugs may inhibit the complement system and thus ameliorate the acute pathological changes induced by immune complexes was investigated. Treatment of fresh human serum with indomethacin (IDM), sulindac (Su), phenylbutazone (Ph) and oxyphenbutazone (OPh) inhibited both the classical and alternative complement (C) pathway activities in a dose-dependent fashion with a 50% inhibition dose of 4.65, 1.0, 1.65 and 1.3 mg/ml respectively. Aspirin, on the other hand, had a comparatively weak anti-complementary activity. Su, Ph and OPh were shown to form complexes with C5, thereby inhibiting the interaction between C3b and C5 and the cleavage of the latter into phlogistic fragments.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D002499:Centrifugation, Density Gradient; D002850:Chromatography, Gel; D003180:Complement C3b Inactivator Proteins; D003182:Complement C5 / Q000037:antagonists & inhibitors; D003169:Complement Inactivator Proteins; D003171:Complement Pathway, Classical / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D046911:Macromolecular Substances; D010113:Oxyphenbutazone / Q000494:pharmacology; D010653:Phenylbutazone / Q000494:pharmacology; D013467:Sulindac / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D003180:Complement C3b Inactivator Proteins; D003182:Complement C5; D003169:Complement Inactivator Proteins; D046911:Macromolecular Substances; D013467:Sulindac; D010653:Phenylbutazone; D010113:Oxyphenbutazone; D001241:Aspirin; D007213:Indomethacin