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Clinical & Experimental Allergy

Effects of erythromycin on experimental extrinsic allergic alveolitis

Authors


Ando First Department of Internal Medicine, Kumamoto University School of Medicine, 1–1-1 Honjo, Kumamoto 860–0811, Japan.

Abstract

Background

Recent clinical studies have demonstrated the efficacy of erythromycin for treating patients with chronic lower respiratory tract inflammation. Mechanisms related to the anti-inflammatory action are yet to be determined.

Objectives

The therapeutic efficacy of erythromycin in experimental extrinsic allergic alveolitis (EAA) was evaluated.

Methods

A murine model of EAA was developed by intratracheal inoculations with particulate Trichosporon mucoides followed by erythromycin or josamycin treatment. Cell populations, specific antibodies, chemotactic activities, TNF-α, IL-1β, MIP-2 and KC of bronchoalveolar lavage fluid (BALF); histopathology of the lung and footpad reaction; myeloperoxidase of the whole lung; and immunohistochemistry of intercellular adhesion molecule-1 (ICAM-1), at 6 and 96 h after the challenge, were examined.

Results

There was a marked neutrophilic alveolitis and bronchiolitis at 6 h, and lymphocytic alveolitis and perivenule cuffing at 96 h after the challenge. Increase in total inflammatory cells and neutrophils in BALF at 6 h was significantly suppressed by pre-treatment with 5 mg/kg/day of erythromycin intraperitoneally for 5 days (P < 0.01), with no apparent effect on specific antibodies, chemotactic activity or cytokines. Erythromycin also suppressed the Arthus-type reaction in the footpad (P < 0.01). Histopathological studies revealed that erythromycin markedly decreased neutrophils in the lung and skin lesions and myeloperoxidase in the lung, simultaneously with inhibiting ICAM-1 expression. The therapy has no remarkable effects on lymphocytes or 96 h response. Josamycin had no effects on the model.

Conclusions

The therapeutic dosage of erythromycin significantly suppressed acute neutrophil influx into the lung, intradermal Arthus reaction and the expression of ICAM-1 in the lesions of experimental EAA. Erythromycin may be effective for treating subjects with acute EAA.

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