Inhibition of neutrophil and eosinophil induced chemotaxis by nedocromil sodium and sodium cromoglycate

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Abstract
1 Neutrophils and eosinophils infiltrate the airways in association with the allergen-induced late phase asthmatic reaction. Mobilization of these cells takes place via lipid-like and protein-like chemotactic factors. In this study platelet-activating factor (PAF), leukotriene B4 (LTB4), zymosan-activated serum (ZAS) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) were used as illustrative examples of both groups. Chemotaxis was studied in human neutrophils and eosinophils. The inhibitory effects of nedocromil sodium and sodium cromoglycate were evaluated. 2 All chemotactic factors tested attracted neutrophils with the following rank order of activity: ZAS > PAF ≡ FMLP ≡ LTB4. Eosinophils were only mobilized by PAF, LTB4 and ZAS with the following rank order of activity: ZAS > PAF > LTB4. 3 Nedocromil sodium and sodium cromoglycate were equally active as the PAF antagonist BN 52021 in inhibiting the PAF-induced chemotaxis of neutrophils (IC50 & 10−8 m). Both drugs were also equally active in inhibiting the chemotaxis of neutrophils induced by ZAS (IC50 ≅ 10−7−10−6 m), FMLP(IC50 ≅ 10−7 m) and LTB4 (IC50 ≅ 10−6 m). 4 Nedocromil sodium significantly inhibited the chemotaxis of eosinophils induced by PAF (IC50 ≅ 10−6 m) and LTB4 (IC50 ≅ 10−7 m). The inhibitory potency of BN 52021 was similar to that of nedocromil sodium on the PAF-induced chemotaxis of eosinophils. Sodium cromoglycate was incapable of eliciting significant inhibition of these chemotactic responses. However, sodium cromoglycate significantly inhibited the chemotaxis of eosinophils induced by ZAS (IC50 ≅ 10−7 m), whereas nedocromil sodium was ineffective.