Leukotriene B₄ as a mediator of early and late reactions to antigen in humans: The effect of systemic glucocorticoid treatment in vivo

The role played by leukotriene B₄ (LTB₄) in human allergic reactions has been the subject of recent interest and speculation. To characterize further the role of this mediator, we quantitated LTB₄ 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 LTB₄ 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 LTB₄ 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 LTB₄ levels. High-performance liquid chromatography analysis of immunoreactive LTB₄ demonstrated that 84% of immunoreactive LTB₄ 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 LTB₄ 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 LTB₄ 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 LTB₄ that they synthesize. These results indicate that human allergic nasal reactions are associated with the release of LTB₄ 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 LTB₄, this mediator may play a complex role in human allergic reactions.