Mechanism of anti-inflammatory action of glucocorticosteroids.
Glucocorticosteroids react with blood monocytes and tissue macrophages to produce a peptide factor which stimulates the random migration of polymorphs in vitro in the capillary-tube migration system. An identical effect on polymorph migration is produced by colchicine and vinblastine, drugs which inhibit the assembly of the cytoplasmic microtubules on which the functional activity of polymorphs depends. Pharmacological agents which inhibit microtubular assembly indirectly by increasing intracellular cyclic adenosine monophosphate (A.M.P.), also stimulate polymorph migration in vitro. These observations suggest that the anti-inflammatory activity of glucocorticosteroid drugs is mediated by a peptide hormone which inhibits polymorph microtubular assembly. Many peptide hormones are believed to act by increasing the concentration of cyclic A.M.P. within target cells and this mechanism is probably also responsible for the inhibitory effect of steroids on phagocytic cells.
D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002465:Cell Movement / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D046508:Culture Techniques; D000242:Cyclic AMP / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006168:Guinea Pigs; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D007424:Intracellular Fluid / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects* / Q000502:physiology; D014747:Vinblastine / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D014747:Vinblastine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D003078:Colchicine