Leukotriene B 4 as a mediator of early and late reactions to antigen in humans: The effect of systemic glucocorticoid treatment in vivo

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The role played by leukotriene B 4 (LTB 4) in human allergic reactions has been the subject of recent interest and speculation. To characterize further the role of this mediator, we quantitated LTB 4 levels in nasal washing by radioimmunoassay in 13 atopic subjects during immediate and late reactions after nasal antigen challenge while the subjects were taking placebo or prednisone (20 mg every 8 hours for 48 hours) in a double-blind, placebo-controlled, crossover protocol and compared these levels with levels of seven nonatopic subjects undergoing similar nasal antigen challenge. Nasal antigen challenge of atopic subjects resulted in an increase in LTB 4 levels during the immediate reaction in 10 of 13 subjects ( 9 13 with a >50% increase over baseline) with no similar increase observed in nonatopic subjects ( p < 0.05). An increase in LTB 4 levels was observed in 12 13 atopic subjects ( 6 13 with >50% increase over a second baseline) during late time periods ( p < 0.05), which was associated with an influx of neutrophils (from 65,000 ± 43,000 to 1,246,000 ± 829,000; p < 0.05). However, nonatopic subjects appeared to demonstrate a similar late increase in LTB 4 levels. High-performance liquid chromatography analysis of immunoreactive LTB 4 demonstrated that 84% of immunoreactive LTB 4 coeluted with the biologically isomer during the immediate reaction, whereas 44% to 61% coeluted with the biologically active isomer during late reactions. Steroid pretreatment had no effect on either the early or late increase in LTB 4 levels or on the neutrophil influx observed during the late reaction. In a second series of studies involving eight subjects, we demonstrated that a single 50 mg oral dose of prednisone had no effect on the release of LTB 4 from neutrophils stimulated ex vivo with calcium ionophore A23187 or serum-activated zymosan, and, furthermore, that neutrophil concentration (“density”) had a marked effect on the ability of neutrophils to metabolize LTB 4 that they synthesize. These results indicate that human allergic nasal reactions are associated with the release of LTB 4 in vivo and that these levels and neutrophil influx are not modified by systemic steroid pretreatment. Because multiple inflammatory cells may participate in these allergic reactions to synthesize and metabolize LTB 4, this mediator may play a complex role in human allergic reactions.