Modulation by nedocromil sodium of immunologic and nonimmunologic activation of monocytes, macrophages, and platelets.
Human monocytes, alveolar macrophages, and blood platelets were used in vitro to investigate the effects of nedocromil sodium on their IgE-dependent stimulation. The drug induced a significant inhibition of the IgE-mediated generation of cytotoxic mediators in both cell populations. This was evidenced by a strong inhibition of the killing of schistosome larvae and decreased free radical production, as demonstrated by chemiluminescence. Nedocromil sodium also produced a significant inhibition of lysosomal enzyme release and synthesis in alveolar macrophages. These effects reached a maximum between 10(-9) and 10(-7) mol/L nedocromil sodium. The 50% inhibition concentration was 10 times lower. The drug was also tested on IgE-activated rat peritoneal macrophages and blood platelets with similar results. Finally, nedocromil sodium was shown to inhibit the abnormal response to aspirin of platelets, both in vitro and ex vivo, from aspirin-sensitive asthma patients.
Centre d'Immunologie et de Biologie Parasitaire, CJF INSERM 90-06, Institut Pasteur, Lille, France.
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Joseph
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Tsicopoulos
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Tonnel
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Capron
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D004347:Drug Interactions; D005609:Free Radicals; D005966:Glucuronidase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000187:drug effects / Q000276:immunology; D007814:Larva / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D017835:Nedocromil; D015539:Platelet Activation / Q000187:drug effects*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D012547:Schistosoma / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005609:Free Radicals; D015363:Quinolones; D017835:Nedocromil; D007073:Immunoglobulin E; D005966:Glucuronidase; D001241:Aspirin