Inhibition of vascular permeability by cycloheximide in granulomatous inflammation

Abstract

The effect of cycloheximide on vascular permeability in proliferative inflammation was investigated by using 8-day-old granuloma pouch induced by carrageenin in rats. The vascular permeability was assayed twice in every rat, immediately before and after the drug treatment with the aid of 125I- and 131I-human serum albumins (HSA) respectively. Leakage of tracers during the period of 30 min, after intravenous injection into the exudate fluid in the granuloma pouch was measured and used as an index of the vascular permeability. The ratio of the leakage values ([ 131I]HSA/[ 125I]HSA) was computed in order to express change of the vascular permeability induced by the drug treatment. Dose-related enhancement in the inhibition of vascular permeability by cycloheximide which was injected directly into the granuloma pouch fluid was evident over the dose range of 0.06–0.6 mg/kg. The time course of the permeability-lowering action was also investigated at a dose of 0.2 mg/kg. The maximum effect was observed at 3 hr after the injection. The permeability-lowering effect disappeared completely by 12 hr. Protein synthesis of the granuloma tissue was also inhibited and changed with time in parallel with the change in the vascular permeability. It was concluded, however, that the fall of the vascular permeability was independent from the inhibition of protein synthesis since puromycin was ineffective for lowering the vascular permeability in the dose which was strongly inhibitory for protein synthesis. The possibility of manifestation of anti-exudative effect through the stimulation of adrenal cortex was also excluded since cycloheximide showed similar activity in intact and adrenalectomized rats.