DELAYED ANTIINFLAMMATORY ACTION OF NEDOCROMIL SODIUM IN THE RAT PAW IS DEPENDENT ON DE-NOVO PROTEIN-SYNTHESIS

Nedocromil sodium is commonly suggested to reduce allergic inflammatio n by inhibiting mediator release from mast cells. However, nedocromil also exhibits a wide range of additional anti-inflammatory activities, including inhibition of increased vascular permeability induced by in dividual mediators such as histamine. In the present study, we have fu rther characterized the mode of action of nedocromil in a rat model fo r hind paw edema. Mast cell-dependent edema was induced with compound 48/80 (edema response mainly due to 5-hydroxytryptamine release), and direct mediator-induced plasma extravasation was evoked by exogenous 5 -hydroxytryptamine (both agents injected locally). Local pretreatment with nedocromil for 20 min dose-dependently inhibited the edema evoked by compound 48/80 more effectively than that induced by 5-hydroxytryp tamine. However, after 2 h pretreatment, both the 5-hydroxytryptamine- and compound 48/80-induced edema responses were inhibited to approxima tely the same extent by a range of concentrations of nedocromil, as we ll as by dexamethasone. Local inhibition of RNA/protein synthesis with actinomycin-D abolished the effects of both dexamethasone and nedocro mil (2 h local pretreatment). We thus conclude that nedocromil can pro duce an 'anti-exudative' effect that is independent of inhibition of m ast cell mediator release, is slow in onset, and requires de novo prot ein synthesis.