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 greater than 50% increase over baseline) with no similar increase observed in nonatopic subjects (p less than 0.05). An increase in LTB4 levels was observed in 12/13 atopic subjects (6/13 with greater than 50% increase over a second baseline) during late time periods (p less than 0.05), which was associated with an influx of neutrophils (from 65,000 +/- 43,000 to 1,246,000 +/- 829,000; p less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Freeland
H S
HS
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md.
Pipkorn
U
U
Schleimer
R P
RP
Bascom
R
R
Lichtenstein
L M
LM
Naclerio
R M
RM
Peters
S P
SP
D000293:Adolescent; D000328:Adult; D000403:Airway Resistance; D005938:Glucocorticoids / Q000494:pharmacology*; D006636:Histamine Release; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000503:physiopathology*; D006969:Hypersensitivity, Immediate / Q000503:physiopathology*; D007975:Leukotriene B4 / Q000502:physiology*; D008875:Middle Aged; D009299:Nasal Provocation Tests; D009504:Neutrophils / Q000502:physiology; D011241:Prednisone / Q000494:pharmacology; D012912:Sneezing
D005938:Glucocorticoids; D007975:Leukotriene B4; D011241:Prednisone