[Possible mechanisms of the anti-inflammatory action of polyamines]

Carrageenin paw edema of rats was inhibited in a dose-dependent manner by subcutaneous administration of polyamines. The latter had to be administered at least 2 hr before carrageenin challenge to achieve such inhibition. Moreover, inhibition was blocked by the simultaneous injection of actinomycin D. Polyamines also inhibited local bluing reactions to histamine in rats and similarly had to be administered 3 hr previously to achieve inhibition. Polyamines were shown to be glucocorticoid-type anti-inflammatory drugs, and may be glucocorticoids mediators of the synthesis of the postulated vascular permeability inhibitory protein that do not inhibit phospholipase A2 activity. Neutrophil chemotaxis was inhibited by polyamines in a concentration-dependent manner. In contrast to the experience with carrageenin paw edema, simultaneous addition to actinomycin D did not block the inhibitory action of polyamines on neutrophil chemotaxis. These results suggest that polyamines possess at least 2 different anti-inflammatory mechanisms. The first is mediated by the synthesis of an anti-inflammatory protein, and the second consist of direct action on leukocytes.