Oxatomide Inhibits the Release of Chemical Mediators from Human Lung Tissues and from Granulocytes

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Abstract
The effects of oxatomide on the release of histamine and leukotriene C4 (LTC4) from human lung fragments and granulocytes were examined and the findings compared with the effects of the antiallergic drugs ketotifen, azelastine and tranilast. Oxatomide inhibited the release of both histamine and LTC4 from human lung fragments in cases of passive sensitization with human IgE myeloma serum upon anti-ε stimulation. IC50 values for the release of LTC4 from human lung fragments were as follows: oxatomide, 2.35 × 10––5M; azelastine, 27.2 × 10––5M; ketotifen, 52.1 × 10––5M; tranilast, 62.9 × 10––5M. Oxatomide also inhibited the release of both histamine and LTC4 from human mixed leukocytes stimulated by the calcium ionophore A23187. IC50 values for the release of LTC4 from human mixed leukocytes were as follows: oxatomide, 1.67 × 10––5M; azelastine, 3.65 × 10––5M; ketotifen, 12.2 × 10––5M; tranilast, 15.1 × 10––5M. The effects of oxatomide on the release of LTC4 from purified human neutrophils and eosinophils were also given attention. Oxatomide inhibited the release of LTC4 from eosinophils more effectively than from neutrophils and mixed leukocytes. As there is evidence that eosinophils play an important role in the development of late asthmatic responses and/or in the aggravation of asthma, oxatomide is expected to be an effective treatment for such conditions.