INHIBITION OF MONOCYTE LEUKOTRIENE B-4 PRODUCTION AFTER ASPIRIN DESENSITIZATION

Aspirin-sensitive patients may be desensitized through a graded series of exposures to aspirin. We investigated the underlying mechanism of aspirin desensitization by measuring the release of leukotrienes B-4 and C-4 from calcium ionophore-stimulated peripheral blood monocytes. Compared with monocytes from normal volunteers (n = 5), monocytes fr om patients with aspirin-sensitive asthma (n = 10) released increased amounts of thromboxane B-2 (1060 +/- 245 pg/ml vs 456 +/- 62 pg/ml), leukotriene B-4 (861 +/- 139 pg/ml vs 341 +/- 44 pg/ml), and leukotriene C-4 (147 +/- 31 pg/ml vs 56 +/- 6 pg/ml) at baseline. After aspirin desensitization, thromboxane B, release was almost completely suppressed in both groups. Leukotriene B, release was significantly decreased in the aspirin-sensitive group (484 +/- 85 pg/ml) but not in the normal subject group (466 +/- 55 pg/ml). The need for prednisone decreased significantly after patients were desensitized to aspirin (10.4 +/- 2.2 mg/day to 1.6 +/- 2.8 mg/day). These results demonstrate that desensitization to aspirin results in decreased monocyte leukotriene B, release. On the basis of the bronchospastic and inflammatory potential of leukotrienes, the decrease in leukotriene release may contribute to the clinical improvement seen after aspirin desensitization.