Animal models for the study of atypical anti-inflammatory agents.

In contrast to the approach focusing on aspirin and cortisone as models for research, a physiopathologically-oriented approach provides the rationale for developing animal models suitable for detecting anti-inflammatory agents with a profile of therapeutic and side effects unlike that of currently used drugs. The so-called 'primary' anti-inflammatory agents have a marked efficacy in animal models of acute inflammation and lack significant anti-PG effects. Clinically, they relieve the symptoms of acute inflammatory conditions, both topically and systemically, are practically inactive in rheumatic disorders and have a profile of side-effects different from that of aspirin or cortisone. Available data suggest that their characteristic profile of side and therapeutic effects reflect qualitative, rather than quantitative differences, from aspirin and cortisone. The so-called 'secondary' anti-inflammatory agents affect the conditioning factors for some inflammatory diseases, including rheumatoid arthritis, rather than the inflammatory process itself. Besides the derangement of the immune system and the consequent development of immunomodulators, the role of specific protein changes as a conditioning factor is discussed and animal models are illustrated focusing on this phenomenon. The possibility is also discussed that protein denaturation is not only responsible for the formation of new antigenic determinants, but also for necrotic lesions accompanying some inflammatory disorders. Results obtained with animal models of conditioned inflammation with marked necrotic lesions are presented. The interest for this approach is that conditioning factors for inflammation appear a more specific target for drug treatment, rather than inflammation itself.