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Erythromycin attenuates an experimental model of chronic bronchiolitis via augmenting monocyte chemoattractant
T Takahashi1, M Suga, A Matsukawa
1First Dept of Internal Medicine, Kumamoto University School of Medicine, Honjo, Japan.
Abstract:
The mechanisms underlying the therapeutic efficacy of erythromycin (EM) in diffuse panbronchiolitis (DPB) was investigated. For this purpose, an experimental rabbit model of DPB induced by Pseudomonas aeruginosa inoculation was employed. Daily administration of EM (3 mg x kg x day(-1)) led to an increase in the number of macrophages in bronchoalveolar lavage fluid (BALF) at an early phase, while reducing the size of granulomatous lesions at the late phase without affecting the number of viable bacteria recovered from the infected lung. Reverse transcriptase polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and immunohistochemical studies showed that monocyte chemoattractant protein (MCP)-1 was produced in both BALF and infected lung. EM treatment resulted in a significant increase in the level of MCP-1 in BALF, while reducing that of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-8. EM also increased MCP-1 messenger ribonucleic acid (mRNA) and protein expression in the infected lung. MCP-1 blockade abolished the protective effect of EM, as neutralization of MCP-1 with anti-MCP-1 antibodies reduced the EM-induced increase in the number of macrophages in BALF, and augmented size of the granulomatous lesions, as compared to control. The results of the present study suggest that erythromycin attenuates the pulmonary granuloma formation, at least in part, by increasing the production of monocyte chemoattractant protein-1.
Insights
Erythromycin (EM) therapy for diffuse panbronchiolitis (DPB) works by increasing monocyte chemoattractant protein-1 (MCP-1), which enhances macrophage recruitment and reduces lung inflammation and granuloma formation.
Area of Science:
- Pulmonology
- Immunology
- Pharmacology
Background:
- Diffuse panbronchiolitis (DPB) is a chronic inflammatory lung disease.
- Erythromycin (EM) is used to treat DPB, but its precise mechanisms are not fully understood.
Purpose of the Study:
- To investigate the therapeutic mechanisms of erythromycin in a rabbit model of diffuse panbronchiolitis.
- To elucidate the role of monocyte chemoattractant protein-1 (MCP-1) in EM's efficacy.
Main Methods:
- An experimental rabbit model of DPB induced by Pseudomonas aeruginosa.
- Administration of EM and assessment of bronchoalveolar lavage fluid (BALF) and lung tissue.
- Techniques included RT-PCR, ELISA, and immunohistochemistry to measure inflammatory mediators.
Main Results:
- EM increased macrophage numbers in BALF and reduced granuloma size, without affecting bacterial load.
- EM significantly elevated MCP-1 levels in BALF and lung tissue.
- EM decreased levels of TNF-alpha, IL-1beta, and IL-8.
- MCP-1 blockade abolished EM's protective effects.
Conclusions:
- Erythromycin attenuates pulmonary granuloma formation in DPB.
- This effect is mediated, in part, by increased production of monocyte chemoattractant protein-1.
- MCP-1 plays a crucial role in the anti-inflammatory and immunomodulatory actions of EM in DPB.
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