NEDOCROMIL SODIUM INHIBITS ANTIGEN-INDUCED CONTRACTION OF HUMAN LUNG PARENCHYMAL AND BRONCHIAL STRIPS, AND THE RELEASE OF SULFIDOPEPTIDE-LEUKOTRIENES AND HISTAMINE FROM HUMAN LUNG FRAGMENTS

The effects of nedocromil sodium on antigen-induced release of sulphidopeptide-leukotrienes and histamine from passively sensitized fragments of human lung, and on antigen-induced contraction of sensitized strips of human lung parenchyma and bronchus, have been studied. Nedocromil sodium 0.1 and 1 μM inhibited leukotriene release from fragments of human lung by 30% and 38% respectively, and histamine release by 43% for both contractions, but 10 μM was ineffective. The lung fragments, which were passively sensitized to house dust mite, Dermataphagoides pteronyssinus, in control experiments released leukotrienes (6.58 ± 0.12 nmol equiv. leukotriene C4 per g, n = 6) and histamine (10.3 ± 1.8% of total tissue histamine, n = 5) when challenged with house dust mite extract. Isolated strips of human lung parenchyma, passively sensitized to D. pteronyssinus, contracted when treated with house dust mite extract to a mean value of 40% of the maximal histamine response for each strip. Nedocromil sodium 0.1 and 1 μM inhibited these contractions by 50% and 70% of the control response, but 10 μM had no inhibitory effect. Isolated rings from human bronchus, also passively sensitized to D. pteronyssinus, contracted when treated with house dust mite extract to a mean value of 86% of the maximal histamine response. Nedocromil sodium 1 μM, but not 0.1 or 10 μM, inhibited contractions by 48% of the control response. The therapeutic effects of nedocromil sodium in allergic asthma may depend, partly, on its inhibition of antigen-induced release of leukotrienes and histamine in human lung and its consequent inhibition of antigen-induced contractions of parenchymal and bronchial tissue.