Plb. Bruijnzeel et al., EFFECTS OF NEDOCROMIL SODIUM ON IN-VITRO INDUCED MIGRATION, ACTIVATION, AND MEDIATOR RELEASE FROM HUMAN GRANULOCYTES, Journal of allergy and clinical immunology, 92(1), 1993, pp. 159-164
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.