Chest
Volume 108, Issue 1, July 1995, Pages 116-122
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Clinical Investigations
Leukotriene B4 in Bronchoalveolar Lavage Fluid of Patients With Diffuse Panbronchiolitis

https://doi.org/10.1378/chest.108.1.116Get rights and content

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.

Section snippets

Patient Population

We studied 9 of 13 patients with DPB (6 men and 3 women; mean age, 37.6 ± 5.4 years; all nonsmokers, shown in Table 1) who were previously described.4 They could be evaluated for both the NCA and the level of LTB4 in the lavage fluid and satisfied the clinical diagnostic criteria for DPB published by the Japanese Ministry of Health and Welfare. These criteria are as follows: (1) symptoms of chronic cough with sputum production and exertional dyspnea; (2) physical signs of coarse crackles and

Lavage Findings Before and After EM Treatment

Table 2 shows the mean values for BAL parameters before and after EM treatment. The mean values for total cell and neutrophil number before EM treatment were significantly higher than those in healthy volunteers (total cell number, 8.10 ± 2.10 × 105/mL vs 2.10 ± 0.75×105/mL, p<0.05; neutrophil number, 6.26 ± 1.92×105/mL vs 0.03 ± 0.01× 105/mL, p<0.05); the values were significantly reduced after EM treatment (Table 2), corresponding with an improvement in clinical symptoms and findings. The

Discussion

The sustained neutrophil accumulation in the airway is a characteristic clinical feature in DPB.3,4 We reported that the accumulation of neutrophils into the respiratory tract of this disease is induced by a variety of chemotactic mediators.4 Thus, we have hypothesized that these mediators, including LTB4, in the lavage fluid induce neutrophil accumulation into the airspace, cause injury to the host by generating the oxidative and proteolytic products of neutrophils, and then could be

Acknowledgment

The authors thank Prof. K. Yamaguchi and Dr. Y. Ishii (Department of Microbiology, Toho University School of Medicine, Tokyo, Japan) for their technical advice and Prof. H. Homma (University of the Air, Chiba, Japan) for his helpful suggestions.

References (31)

  • KudohS et al.

    Clinical effect of low-dose long-term erythromycin chemotherapy on diffuse panbronchiolitis

    Jpn J Thorac Dis

    (1987)
  • KadotaJ et al.

    A mechanism of erythromycin treatment in patients with diffuse panbronchiolitis

    Am Rev Respir Dis

    (1993)
  • Ford-HutchinsonAW et al.

    Leukotriene B4, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes

    Nature

    (1980)
  • GoetzlEJ et al.

    Novel structural determinants of the human neutrophil chemotactic activity of leukotriene B

    J Exp Med

    (1981)
  • PalmerRMJ et al.

    Release of leukotriene B4 from human neutrophils and its relationship to degranulation induced by N-formyl-methionyl-leucyl-phanylalanine, serum-treated zymosan and the ionophore A23187

    Immunology

    (1983)
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