title: Nedocromil sodium and airway inflammation in vivo and in vitro.
abstract: We conducted a series of studies investigating the antiinflammatory effects of nedocromil sodium, with particular reference to its effects on human bronchial epithelial cells and eosinophils in vitro and on eosinophils in vivo. Nedocromil sodium produced a dose-related inhibition of ozone-induced IL-8 release from human bronchial epithelial cells and also attenuated the release of granulocyte macrophage colony-stimulating factor, tumor necrosis factor-alpha, and soluble intercellular adhesion molecule 1. The culture medium from human bronchial epithelial cell cultures, containing the proinflammatory cytokines IL-8, granulocyte 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 cultured human endothelial cells. The chemotaxis and increased adhesion were blocked in the presence of nedocromil sodium. The drug also abrogated the epithelial cell dysfunction (assessed as ciliary beat frequency) induced by the presence of activated eosinophils and blocked the release of eosinophil cationic protein from the eosinophils. We also conducted a double-blind placebo-controlled study of the effects of regular albuterol 200 micrograms 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 activated eosinophils in biopsy samples, inflammation decreased with nedocromil sodium and was significantly different from a deterioration with albuterol, although neither of these changes was significantly different from that with placebo treatment. Levels of eosinophil cationic protein in bronchoalveolar lavage samples showed a similar trend.
authors.affiliation: Department of Asthma and Allergic Respiratory Diseases, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London Chest Hospital, United Kingdom.
authors.forename: J L
authors.initials: JL
authors.lastname: Devalia
authors.forename: C
authors.initials: C
authors.lastname: Rusznak
authors.forename: M M
authors.initials: MM
authors.lastname: Abdelaziz
authors.forename: R J
authors.initials: RJ
authors.lastname: Davies
mesh_terms: D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000166:cytology; D016535:Bronchial Hyperreactivity / Q000517:prevention & control*; D004847:Epithelial Cells; D006801:Humans; D018836:Inflammation Mediators / Q000627:therapeutic use; D017835:Nedocromil / Q000627:therapeutic use*
chemical_list: D018836:Inflammation Mediators; D017835:Nedocromil