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

Background-The cysteinyl-leukotrienes (LTC4, LTD4, LTE4) are critical bronc hoconstrictor and eosinophilotactic mediators in asthma while LTB4 is a pot ent neutrophil chemoattractant. Glucocorticosteroids are front line antiinf lammatory treatment for asthma but the evidence that they reduce leukotrien e (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 cal cium ionophore stimulated blood leucocytes and bronchoalveolar lavage (BAL) cells of eight normal subjects and eight patients with mild allergic asthm a 4-6 hours after intravenous administration of a single 100 mg dose of met hylprednisolone. Results-Ionophore stimulated synthesis of LTC4 (but not LTB4) in blood gran ulocytes tended to be higher in asthmatic subjects (mean 9.7 ng/10(6) cells ) than in normal subjects (4.2 ng/10(6) cells; p = 0.08) and intravenous me thylprednisolone reduced synthesis of LTC4 (but not LTB4) to normal levels (2.9 ng/10(6) cells; 95% CI for the reduction 1.0 to 12.5 ng/10(6) cells; p = 0.03). In blood mononuclear cells methylprednisolone reduced LTC, synthe sis in asthmatic subjects from 1.26 to 0.79 ng/10(6) cells (95% CI for the reduction 0.26 to 0.79, p = 0.014) and tended to reduce LTC4 synthesis in n ormal subjects from 1.51 to 0.86 ng/10(6) cells (p = 0.08). Methylprednisol one 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 ce lls from either group nor on LT levels in BAL fluid. Conclusions-Intravenous methylprednisolone can reduce synthesis of leukotri enes in blood granulocytes and mononuclear cells within six hours of a sing le intravenous dose.