NEDOCROMIL SODIUM AND AIRWAY INFLAMMATION IN-VIVO AND IN-VITRO

We conducted a series of studies investigating the antiinflammatory ef fects of nedocromil sodium, with particular reference to its effects o n human bronchial epithelial cells and eosinophils in vitro and on eos inophils in vivo. Nedocromil sodium produced a dose-related inhibition of ozone-induced IL-8 release from human branchial epithelial cells a nd also attenuated the release of granulocyte macrophage colony-stimul ating factor; tremor necrosis factor-alpha, and soluble intercellular adhesion molecule 1. The culture medium from human bronchial epithelia l cell cultures, containing the proinflammatory cytokines IL-8, granul ocyte macrophage colony-stimulating factor, ''regulated on activation normal T expressed and secreted'' IL-1 beta, and tumor necrosis factor -alpha, increased eosinophil chemotaxis and eosinophil adhesion to cul tured human endothelial cells. The chemotaxis and increased adhesion w ere blocked in the presence of nedocromil sodium. The drug also abroga ted the epithelial cell dysfunction (assessed as ciliary beat frequenc y) induced by the presence of activated eosinophils and blocked the re lease of eosinophil cationic protein fram the eosinophils. We also con ducted a double-blind placebo-controlled study of the effects of regul ar albuterol 200 mu g or nedocromil sodium 4 mg, both given four times daily for 16 weeks, on inflammatory cell numbers in bronchial biopsy and bronchoalveolar lavage samples. Assessed in terms of total and act ivated eosinophils in biopsy samples, inflammation decreased with nedo cromil sodium and was significantly different from a deterioration wit h albuterol, although neither of these changes was significantly diffe rent from that with placebo treatment. Levels of eosinophil cationic p rotein in bronchoalveolar lavage samples showed a similar trend.