Norbert Gruenfeld

Chapter 25. Non-steroidal Anti-inflammatory Agents

Publisher Summary This chapter elaborates the development and clinical studies of nonsteroidal anti-inflammatory agents. The studies of the possible role of infectious inductions and/or adverse immunological reactions continue with the hope of defining the trigger mechanism for the chronic and self-perpetuating inflammatory processes in man. Under suitable experimental conditions, all major nonsteroidal anti-inflammatory drugs inhibit the multiplication of different viruses in cell cultures. The synthetic polyanionic pyran copolymer induces interferon and inhibits adjuvant-induced arthritis in rats. These data suggest that a virus may be implicated in the pathogenesis of adjuvant-induced polyarthritis. The constituents of the kinin system in rheumatoid arthritic joints show that higher synovial fluid of polyarthritic joints are mainly derived from plasma and not from invading leucocytes. Trasylol, a trypsin-kallikrein inhibitor, exerts an anti-inflammatory effect against acute urate-induced arthritis in rabbits. Filipin, a potent lysosomal membrane labilizer both in vitro and in vivo , is known to induce chronic degenerative joint diseases in rabbits.

Chapter 19. Non-steroidal Anti-inflammatory Agents

Publisher Summary This chapter elaborates studies analyzing non-steroidal anti-inflammatory agents. The importance of the circulating lymphocyte in association with the auto-immune component of adjuvant disease was shown by studies with heterologous antirat lymphocyte serum which prevents secondary responses to complete adjuvant. The RNA/DNA ratio of the lymphocyte may be a useful means of measuring immunological activity of an agent. The theory that enzymes released from lysosomes may denature the native constituents of cells of connective tissue and induce the formation of circulating antibodies as part of the normal immune response appears to be a strong possibility in the adjuvant disease of the rat. The increase in serum lysozyme levels observed in the polyarthritic rat may reflect the release of enzymes from leukocytic cells of the inflamed areas into the circulation. Phenylbutazone and indomethacin were found to be effective in preventing such increases. An impressive number of arylacetic and aryl-alkanoic acids with significant anti-inflammatory properties were reported. Myalex ® (ICI 54450) was clinically effective in rheumatoid arthritis. Activity was also reported for 5- p -chlorophenyl-2-furanacetic acid. In another study, anti-inflammatory activity was claimed for phenylacetic acids substituted in the 4-position by heterocyclic systems, pyrryl, phenyl, and benzoyl.