The effect of indomethacin on immunologic release of histamine and sulfidopeptide leukotrienes from human bronchus and lung parenchyma

We studied the effect of indomethacin on immunologic mediator release from human bronchial tissue (n = 6) and lung parenchyma (n = 7). Tissues were obtained from surgical specimens, minced, passively sensitized, and challenged with antigen E or anti-IgE in the presence or absence of indomethacin. At maximal levels of immunologic stimulation with either antigen or anti-IgE, the bronchial and parenchymal tissues released approximately 5 and 20% of total histamine (net), respectively, and approximately 3.5 and 45 ng/g of immunoreactive sulfidopeptide leukotriene, respectively. Analysis by high performance liquid chromatography followed by radioimmunoassay revealed that the airway supernatants contained LTD4 and LTE4, whereas the lung parenchymal samples contained predominantly LTE4. Little or no LTC4 was detected in either airway or parenchymal samples. Incubation with indomethacin (5 x 10(-6) M) resulted in approximately a 3-fold increase in antigen or anti-IgE-induced release of leukotrienes from the bronchial tissue. Indomethacin also enhanced antigen-induced histamine release approximately 2-fold but had no effect on anti-IgE-induced histamine release from this tissue. In contrast, indomethacin had no effect on antigen or anti-IgE-induced histamine or leukotriene release from the lung parenchymal tissue at any level of immunologic stimulation. These results support the hypothesis that indomethacin enhances human anaphylactic bronchospasm in vitro through an increase in mediator release from bronchial mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)