EFFECTS OF NEDOCROMIL SODIUM ON IN-VITRO INDUCED MIGRATION, ACTIVATION, AND MEDIATOR RELEASE FROM HUMAN GRANULOCYTES

Using the allergen-induced late-phase asthmatic reaction as a working model, we studied the activity of certain inflammatory cells and their reaction to nedocromil sodium. The processes that were examined in vi tro included the following: the chemotaxis of purified neutrophils and eosinophils, the early steps of neutrophil and eosinophil activation, and the release of mediators from these cells. Nedocromil sodium stro ngly inhibited neutrophil mobilization caused by four chemotactic fact ors (zymosan activated serum, N-formyl-methionyl-leucyl-phenylalanine platelet-activating factor PAF!, and leukotriene B4 LTB4! and eosino phil mobilization caused by two factors (PAF and LTB4). In vitro treat ment of eosinophils from normal subjects with picomolar concentrations of interleukin-3, interleukin-5, or granulocyte-macrophage colony sti mulating factor increased the chemotactic responsiveness toward PAF an d LTB4 and induced a chemotactic responsiveness toward N-formyl-methio nyl-leucyl-phenylalanine and neutrophil activating factor/interleukin- 8. The zymosan activated serum-induced chemotactic responsiveness rema ined unaltered. Nedocromil sodium inhibited the cytokine-primed chemot actic responsiveness to the various chemotaxins, not the influence of the cytokines on the cells. Activation of granulocytes, as measured by Ca2+ influx, was not inhibited by nedocromil sodium. Mediator formati on in eosinophils was modified only slightly. These results suggest th at inhibiting the mobilization of inflammatory cells in the lung tissu e may be an important action of nedocromil sodium. Therefore these eff ects may be relevant to the treatment of asthma given the role of airw ay inflammation in this disease process.