Effect of intravenous corticosteroid on ex vivo leukotriene generation by blood leucocytes of normal and asthmatic patients

Abstract

Background - The cysteinyl-leukotrienes (LTC4, LTD4, LTE4) are critical bronchoconstrictor and eosinophilotactic mediators in asthma while LTB4 is a potent neutrophil chemoattractant. Glucocorticosteroids are front line antiinflammatory treatment for asthma but the evidence that they reduce leukotriene (LT) synthesis in vivo is poor. Methods - In a randomised, double blind, placebo controlled, crossover trial immunoassays were used to measure ex vivo synthesis of LTC4 and LTB4 by calcium ionophore stimulated blood leucocytes and bronchoalveolar lavage (BAL) cells of eight normal subjects and eight patients with mild allergic asthma 4-6 hours after intravenous administration of a single 100 mg dose of methylprednisolone. Results - Ionophore stimulated synthesis of LTC4 (but not LTB4) in blood granulocytes tended to be higher in asthmatic subjects (mean 9.7 ng/106 cells) than in normal subjects (4.2 ng/106 cells; p = 0.08) and intravenous methylprednisolone reduced synthesis of LTC, (but not LTB4) to normal levels (2.9 ng/106 cells; 95% CI for the reduction 1.0 to 12.5 ng/106 cells; p = 0.03). In blood mononuclear cells methylprednisolone reduced LTC4 synthesis in asthmatic subjects from 1.26 to 0.79 ng/106 cells (95% CI for the reduction 0.26 to 0.79, p = 0.014) and tended to reduce LTC, synthesis in normal subjects from 1.51 to 0.86 ng/106 cells (p = 0.08). Methylprednisolone also significantly reduced synthesis of LTB4 in mononuclear cells from both subject groups (p = 0.014). It had no effect on LT synthesis in BAL cells from either group nor on LT levels in BAL fluid. Conclusions - Intravenous methylprednisolone can reduce synthesis of leukotrienes in blood granulocytes and mononuclear cells within six hours of a single intravenous dose.