Effects of ONO-1078 (pranlukast) on cytokine production in peripheral blood mononuclear cells of patients with bronchial asthma

Background ONO-1078 (pranlukast) is a leukotriene receptor antagonist devel oped in Japan. This drug has been shown to be useful in oral treatment of b ronchial asthma, The present study was undertaken to assess the effects of this drug on the production of cytokines in the peripheral blood mononuclea r cells of patients with asthma under stimulation with specific antigens. Methods Peripheral blood mononuclear cells from mite antigen-positive asthm atic patients (immunoglobulin E RAST score > 3) were incubated for 72 h in the presence of mite antigen (10 mu g/mL). The supernatant of the culture w as subjected to enzyme-linked immunosorbent assay (ELISA) to quantify inter leukin (IL)-4, IL-3, IL-5, and granulocyte macrophage-colony stimulating fa ctor (GM-CSF). Other peripheral blood mononuclear cells from the same patie nts were incubated for 72 h in the presence of both mite antigen (10 mu g/m L) and ONO-1078 (0.5, 1, or 10 mu g/mL), followed by ELISA of the supernata nt to quantify the cytokines. Results Production of IL-4, IL-5, and GM-CSF by mononuclear cells under sti mulation with mite antigen was markedly suppressed when they were exposed t o ONO-1078 at a concentration of 10 mu g/mL. Conclusion The results suggest that ONO-1078 acts directly on peripheral bl ood mononuclear cells and that blockade of leukotriene receptors on blood m ononuclear cells by the cysteinyl-leukotriene receptor antagonist (LTRA) pr anlukast (ONO-1078) can dose-dependently inhibit release of immunoreactive TH2-type cytokines (IL-3, IL-4, GM-CSF, and possibly IL-5), but not of the TH1-type cytokine IL-2, when stimulated by mite allergen in vitro. The data may provide clues to the mechanism by which a number of LTRA including zaf irulukast and montelukast can reduce airway, sputum and blood eosinophil co unts in clinical asthma. It supports animal studies showing that anti-IL-5 antibodies partially block cys-LT-induced airway eosinophilia, suggesting t hat cys-LTs may cause secondary release of IL-5 from an unknown cell-type. These findings indicate that ONO-1078 suppresses the production of IL-4 (a cytokine that affects IgG antibody production), IL-5, and GM-CSF (cytokines that affect eosinophil activation) by peripheral blood mononuclear cells u nder stimulation with specific antigens in patients with bronchial asthma. Because of its anti-inflammatory effects, ONO-1078 should be useful in the treatment of bronchial asthma.