Leukotriene B4 in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis.
Leukotriene B4 (LTB4) is a potent proinflammatory mediator that may be of particular relevance to the pathology of several respiratory diseases. We have previously reported that neutrophil chemotactic mediators in the lavage fluid of patients with diffuse panbronchiolitis (DPB) consist of many components. In this study, we evaluated the effect of erythromycin (EM) on the pathogenesis of DPB, by examining the level of LTB4 in the bronchoalveolar lavage (BAL) fluid, and determining the relationship between the level and neutrophil accumulation into the respiratory tract. Pre-EM treatment neutrophil chemotactic activity (NCA) in the patients with DPB was significantly increased compared with that in five healthy nonsmoking volunteers (HVs) (p < 0.001), and the level was markedly reduced after EM treatment (p < 0.001). The amounts of LTB4, detected in the BAL fluid from the patients, was also significantly higher than those in control subjects (3.5 +/- 1.1 ng/mL vs 0.1 +/- 0.0 ng/mL, p < 0.001), and the level was significantly reduced after EM treatment (0.6 +/- 0.3 ng/mL, p < 0.01). In addition, the percent reduction of the level of LTB4 was significantly correlated with NCA (r = 0.832, p < 0.01); the reduction was also significantly correlated with neutrophil percentage before and after EM treatment (r = 0.778, p < 0.05). These findings provide evidence for the potent role of LTB4 in the respiratory tracts of patients with DPB and suggest that this lipoxygenase metabolite is involved in the recruitment of neutrophils into the airways of the patients. Our findings suggest that LTB4 is one of the most important chemotactic mediators that has a pathogenetic role in the airway damage of DPB. Erythromycin might inhibit the production of this mediator, restrict the neutrophil accumulation, modulate the excessive inflammation in the respiratory tract, and ultimately improve the pathogenesis of DPB.
Oda
H
H
Second Department of Internal Medicine, Nagasaki University School of medicine, Japan.
Kadota
J
J
Kohno
S
S
Hara
K
K
D000328:Adult; D001988:Bronchiolitis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002634:Chemotaxis, Leukocyte; D004917:Erythromycin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007975:Leukotriene B4 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects; D012129:Respiratory Function Tests
D007975:Leukotriene B4; D004917:Erythromycin