Effects of ZCR-2060 on Allergic Airway Inflammation and Cell Activation in Guinea-pigs

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Abstract
— The effects of 2‐(2‐(4‐(diphenylmethyl)‐1‐piperadinyl) ethoxy) benzoic acid malate (ZCR‐2060) on allergic airway inflammation and inflammatory cell activation in guinea‐pigs were studied. Allergic airway inflammation was induced by inhalation of antigen into actively‐sensitized animals and the increase in inflammatory cells into bronchoalveolar lavage fluid (BALF) was measured. Aeroantigen‐induced infiltration of inflammatory cells, especially eosinophils and neutrophils, in BALF gradually increased, and reached a peak at 6 or 9 h after the challenge. ZCR‐2060 (1 mg kg−1 p.o.) clearly inhibited the increase of eosinophil numbers in BALF. Moreover, the effect of ZCR‐2060 on inflammatory cell activation in terms of chemotaxis and superoxide generation in‐vitro was studied. ZCR‐2060 (10−6‐10−4 m) inhibited the platelet‐activating factor (PAF)‐induced chemotaxis of eosinophils and neutrophils, but did not inhibit the leukotriene B4‐induced chemotaxis of eosinophils and the formyl‐Met‐Leu‐Phe‐induced chemotaxis of neutrophils. PAF‐induced superoxide anion generation by eosinophils, neutrophils and alveolar macrophages was inhibited by ZCR‐2060 (10−6‐10−4 m). However, ZCR‐2060 did not affect phorbol myristate acetate‐induced superoxide anion generation by eosinophils, neutrophils and alveolar macrophages. These results indicate that ZCR‐2060 inhibits allergic airway inflammation, and PAF‐induced inflammatory cell activation in guinea‐pigs. ZCR‐2060 may prove useful for the treatment of allergic airway inflammation or allergic disorders, especially inflammatory cell infiltration and activation.

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