, Volume 42, Issue 1-2, pp 50-55

Antirheumatic drug profiles evaluated in the adjuvant arthritis of rats by multiparameter analysis

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Abstract

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 cyclo-sporin 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. Quantitative improvement of certain parameters by indometacin was easily differentiated from unchanged disease parameters.

Thus, the complex set of pharmacological data provided by the rat FAA model was visually displayed by the multiparameter spider scheme, allowing a more rapid and easier comprehension of antirheumatic drug profiles.