Interleukin-13, but Not Indomethacin, Increases Cysteinyl-Leukotriene Synthesis in Human Lung Macrophages

Abstract

Aspirin-exacerbated respiratory disease (AERD) is associated with constitutively elevated synthesis of bronchoconstrictor cysteinyl-leukotrienes, associated with increased expression of leukotriene (LT)C₄ synthase and Th2 cytokines and airway eosinophilia. We examined whether interleukin-13 can increase LTC₄ synthase gene transcription and cysteinyl-leukotriene synthesis in macrophages isolated from resected human lung tissue and whether an NSAID (indomethacin) can trigger further cysteinyl-leukotriene synthesis in these cells. Overnight culture of human lung macrophages with IL-13 (10 ng/mL) increased spontaneous and ionophore-stimulated production of cysteinyl-leukotrienes by 42% (P=0.02) and 52% (P=0.005), respectively, as quantified by enzyme immunoassays, but PCR gene transcription assays did not demonstrate an effect on LTC4S mRNA. The addition of indomethacin (100 μM) did not modulate cysteinyl-leukotriene production in either IL-13-treated or untreated macrophages. We conclude that while IL-13 enhances cysteinyl-leukotriene synthesis in human lung macrophages, it does not replicate the enhanced LTC₄ synthase expression observed in the AERD lung nor confer sensitivity to NSAIDs.