Immunologic effects of nonsteroidal anti-inflammatory agents

The information reviewed allows us to reassess our previously held assumption that NSAIAs work by removing 'proinflammatory' prostaglandins. However, it does not allow us to deduce the real mechanism of action of these drugs. Perhaps NSAIAs work in part by inhibiting rheumatoid factor production by 'depressing' suppressor cell function in the synovium. Perhpas they work by inhibiting the release of collagenase from monocytes or by inhibiting neutrophil migration and activation. Perhpas all of these mechanisms are involved. Perversely, many of the immunologic effects of NSAIAs may very well be detrimental to patients with rheumatoid arthritis, particularly as regards the stimulation of cytotoxicity. However, it should be clear to any clinician, that NSAIAs, whatever their mechanism or mechanisms of action, are therapeutically less than optimal in the patient with rheumatoid arthritis. If they are more than palliative, it is not overwhelmingly obvious. The importance of determining the mechanism of action of NSAIAs is clear, for we cannot intelligently and efficiently design more efficacious or less toxic drugs without an understanding of the mechanisms of efficacy and toxicity of drugs currently in use. Without such knowledge, the search for better agents is reduced to serendipity.