Antirheumatic drug profiles evaluated in the adjuvant arthritis of rats by multiparameter analysis.
Freund's adjuvant arthritis (FAA) in susceptible rats (male, Lewis strain) is a well-established experimental model of rheumatoid arthritis to evaluate inherent drug properties, i.e. anti-inflammatory and/or immunosuppressive/immunomodulatory properties which are only ascertained by combining multiple parameter analysis. We employed a synoptic multiparametric evaluation system for the multifaceted FAA, a so-called "spider scheme", to facilitate a more rapid and easier comparison of qualitative and quantitative drug properties by visual display than that achieved by mere tabulation of the data. The spider scheme comprised six well-established parameters to evaluate the FAA disease (primary and secondary hind paw swelling, arthritic index which included macroscopic alterations of non-injected paws, nose, ears and tail, body weight changes and relative organ weights of thymus and spleen). By calculation of an index as a percent change in comparison to control and untreated diseased animals, the degree of improvement or impairment of the FAA by a tested compound could easily be entered into the spider scheme. The FAA parameter spider scheme clearly differentiated the most beneficial immunomodulatory properties of cyclosporin A from those of the immunosuppressive agents dexamethasone and cyclophosphamide as well as from the mere anti-inflammatory cyclooxygenase inhibitors. Among this latter class of non-steroidal anti-inflammatory compounds, a similar profile was demonstrated for indometacin and diclofenac, as well as for tenidap, which is claimed to have cytokine-modulating properties, as reflected by the reduction of acute-phase proteins in patients with rheumatoid arthritis. Yet, in this FAA model, with tenidap, no additional qualitative drug properties could be discerned.(ABSTRACT TRUNCATED AT 250 WORDS)
Theisen-Popp
P
P
Bayer A. G. Wuppertal, Germany.
Müller-Peddinghaus
R
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology*; D001835:Body Weight / Q000187:drug effects; D004008:Diclofenac / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005528:Foot / Q000473:pathology; D005620:Freund's Adjuvant; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D013256:Steroids
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D013256:Steroids; D004008:Diclofenac; D005620:Freund's Adjuvant; D007213:Indomethacin