Erythromycin attenuates an experimental model of chronic bronchiolitis via augmenting monocyte chemoattractant protein-1.
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.
Takahashi
T
T
First Dept of Internal Medicine, Kumamoto University School of Medicine, Honjo, Japan.
Suga
M
M
Matsukawa
A
A
Sato
K
K
Okamoto
T
T
Ichiyasu
H
H
Ohkawara
S
S
Yoshinaga
M
M
Ando
M
M
D000818:Animals; D001988:Bronchiolitis / Q000188:drug therapy* / Q000276:immunology; D018932:Chemokine CCL2 / Q000502:physiology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004917:Erythromycin / Q000627:therapeutic use*; D008297:Male; D011817:Rabbits
D018932:Chemokine CCL2; D004917:Erythromycin