Inhibitory effects of lodoxamide on eosinophil activation.
Recent reports describe the beneficial use of lodoxamide, an anti-allergic compound, for the treatment of asthma and allergic conjunctivitis. Lodoxamide is known as a mast cell stabilizer, however, the association of a significant clinical improvement with a specific decrease in eosinophil infiltrate suggested possible direct effects of lodoxamide on eosinophils. The chemotactic response of eosinophils to fMLP as well as to IL-5, in vitro, was very significantly and dose-dependently inhibited by Lodoxamide. Lodoxamide was also able to strongly inhibit the release of eosinophil peroxidase after IgA-dependent activation and, to a lesser extent, the release of eosinophil cationic protein and eosinophil-derived neurotoxin. Moreover, the release of cytotoxic mediators evaluated in an antibody-dependent cytotoxicity assay against parasitic targets was also significantly reduced, not only in the case of human eosinophils but also in a rat eosinophil-mast cell model of cytotoxicity. Taken together, these results indicate that lodoxamide can exert potent inhibitory effects on eosinophil activation in vitro combined with a strong inhibition of eosinophil attraction, leading therefore to a reduction in their pathological potential in vivo.
Capron
M
M
Unité INSERM U 167, Institut Pasteur, Lille, France. monique.capron@pasteur-lille.fr
Loiseau
S
S
Papin
J P
JP
Robertson
S
S
Capron
A
A
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D001798:Blood Proteins / Q000187:drug effects / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D047091:Eosinophil Granule Proteins; D047209:Eosinophil Peroxidase; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D010072:Oxamic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010544:Peroxidases / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012260:Ribonucleases
D018926:Anti-Allergic Agents; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D011506:Proteins; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases; D010072:Oxamic Acid; C021702:lodoxamide ethyl