Problems and results in testing the possible mode of anti-inflammatory glucocorticoid action in carrageenin rat paw oedema: advantages of local substance injection.

The anti-inflammatory effect of dexamethasone in carrageenin rat paw oedema was significantly reduced or abolished by local injection of 0.5-2.5 mg of the antiglucocorticoid progesterone, or of 5 micrograms cycloheximide, or of 2.5 micrograms actinomycin D, into the oedematous area. The results point to indirect dexamethasone action via receptor occupation and de novo protein synthesis, but this view could not be undoubtedly confirmed by systemic administration of essentially higher doses of the substances. The advantages of local low dose antagonist administration versus systemic injection of higher doses are mainly the production of effective tissue levels, as well as avoidance of toxic and other side-effects.