Effect of intravenous corticosteroid on ex vivo leukotriene generation by blood leucocytes of normal and asthmatic patients.
BACKGROUND
The cysteinyl-leukotrienes (LTC(4), LTD(4), LTE(4)) are critical bronchoconstrictor and eosinophilotactic mediators in asthma while LTB(4) is a potent neutrophil chemoattractant. Glucocorticosteroids are front line anti-inflammatory 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 LTC(4) and LTB(4) 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 LTC(4) (but not LTB(4)) in blood granulocytes 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 methylprednisolone reduced synthesis of LTC(4) (but not LTB(4)) 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(4) synthesis 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 LTC(4) synthesis in normal subjects from 1.51 to 0.86 ng/10(6) cells (p = 0.08). Methylprednisolone also significantly reduced synthesis of LTB(4) 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.
Hood
P P
PP
Department of Respiratory Medicine, King's College School of Medicine & Dentistry, London SE5 9PJ, UK.
Cotter
T P
TP
Costello
J F
JF
Sampson
A P
AP
D000287:Administration, Topical; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D001999:Bronchoscopy; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D007262:Infusions, Intravenous; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D015289:Leukotrienes / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D008775:Methylprednisolone / Q000378:metabolism / Q000627:therapeutic use*; D006113:United Kingdom
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D015289:Leukotrienes; D008775:Methylprednisolone