Inhibition of eosinophil density change and leukotriene C4 generation by nedocromil sodium.
Nedocromil sodium (NS) has been shown to inhibit the late asthma response to inhaled antigen and to control symptoms in chronic asthma; in both processes the eosinophil is thought to be an important contributor. To understand the antiinflammatory actions of NS in asthma, its effects on three eosinophil functions were evaluated: (1) change in cell density during in vitro culture, (2) synthesis of leukotriene C4 (LTC4), and (3) generation of superoxide anion. In these studies normal density (greater than 1.095 gm/ml) purified human peripheral blood eosinophils were cultured for 24 hours in 50% conditioned medium from cow pulmonary arterial endothelial cells. After incubation, 45.2% +/- 8.0% of the eosinophils had a density less than 1.085 gm/ml. In the presence of NS (10 mumol/L), only 32.0% +/- 7.3% became less dense (p = 0.0393). In contrast, NS had no effect on changes in cell density after a 20-minute exposure of eosinophils to functional activators N-formyl-methionyl-leucyl-phenylalanine (0.1 mumol/L) or platelet activating factor (0.1 mumol/L). Furthermore, calcium ionophore-activated LTC4 secretion was found to be significantly inhibited by NS (3.8 +/- 0.6 ng/ml vs. 2.4 +/- 0.3 ng/ml with 1 mumol/L NS or 1.7 +/- 0.6 ng/ml with 10 mumol/L NS, p less than 0.025). However, NS did not significantly alter eosinophil superoxide anion generation. The effects of NS on eosinophil function suggest a mechanism by which this medication may be effective in asthma, particularly in the regulation of the late asthmatic response. Furthermore, the selective regulatory effects of NS may also provide insight into the biologic activities of eosinophils.
Sedgwick
J B
JB
Department of Medicine, University of Wisconsin Medical School, Madison.
Bjornsdottir
U
U
Geiger
K M
KM
Busse
W W
WW
D000328:Adult; D000838:Anions / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002452:Cell Count / Q000187:drug effects; D004804:Eosinophils / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D017835:Nedocromil; D015363:Quinolones / Q000494:pharmacology*; D013189:SRS-A / Q000096:biosynthesis*; D013481:Superoxides / Q000378:metabolism
D000838:Anions; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015363:Quinolones; D013189:SRS-A; D017835:Nedocromil; D013481:Superoxides