A comparison of the carrageenan edema test and ultraviolet light-induced erythema test as predictors of the clinical dose in rheumatoid arthritis

Abstract

Twelve non-steroidal anti-inflammatory agents (NSAI's) and one steroidal anti-inflammatory agent, dexamethasone, were examined in the carrageenan edema test (CET) in the rat and in the ultraviolet light-induced erythema test (UVE) in the guinea pig to evaluate the correlation between those models of inflammation and the clinical dose of the NSAI's in the treatment of rheumatoid arthritis. The regression of the logarithm of the clinical dose with the logarithm of the ED50 for UVE gave a slope of 0.54 implying a non-parallelism of assays and a difference in mechanism. Dexamethasone failed to inhibit the UVE thereby corroborating this point. The parallelism of the logarithm of the clinical dose with the logarithm of the ED50 for the CET was substantially better (slope = 0.86). Dexamethasone was active in CET and its dose would be predicted by the CET regression. When only one variable was used for a prediction, log(CET) was a better predictor of log (clinical dose) than log(UVE). Standard methods for best regression selection indicated that even when both predictor variables were considered, log(CET) alone gave the best regression equation for predicting clinical dose. The view that inhibition of prostaglandin biosynthesis is the primary anti-inflammatory mechanism of NSAI's in rheumatoid arthritis is discussed in terms of these findings.