Effect of nedocromil sodium on microvascular leakage

The recognition that asthma is a chronic inflammatory disease has focused attention on microvascular leakage, which is a component of the inflammatory process. Epithelial shedding, airway edema, increased airway resistance, and airway hyperresponsiveness can result from the plasma extravasation caused by leakage. The chain of inflammatory events set off by microvascular leakage may contribute to the development of the late-phase asthmatic response. Thus the search for drugs that ameliorate this leakage continues. Intravenous nedocromil sodium in a dose of 100 micrograms/kg is effective in blocking microvascular leakage induced by intravenous allergen in sensitized guinea pigs but has no effect on leakage induced by either intravenous histamine or platelet-activating factor, which suggests that it acts predominantly on mediator release. Studies in hamsters, however, have demonstrated that nedocromil sodium is effective in blocking leakage induced by histamine, which acts directly on endothelial cells. The ability of nedocromil sodium to reduce microvascular leakage may contribute to its effectiveness in preventing the late-phase response, but the mechanism by which this reduction occurs is not completely understood.