Nonspecific action of glucocorticosteroids after high-dose pulse therapy?

The original view of glucocorticoid effects as being divided into physiological and pharmacological ones is no longer acceptable, i.e. all glucocorticoid effects are apparently mediated by receptor occupation which triggers RNA protein synthesis. The concentrations needed for receptor-mediated effects are low, e.g. the KD value for dexamethasone is in the nanomolar range. The high-dose pulse glucocorticoid therapy results in blood concentrations much higher than those necessary for receptor saturation. This makes sense only when nonspecific effects may be expected to occur which necessitate concentrations higher than 10(-6) mol.l-1. In this paper the question of nonspecific glucocorticoid effects in adjuvant arthritis and carrageenin paw edema of rats was investigated using the glucocorticoid receptor antagonist RU 38486 and by injecting the RNA/protein synthesis inhibitors actinomycin D or cycloheximide. We did not find convincing evidence for nonspecific glucocorticoid mechanisms.