Effects of erythromycin on experimental extrinsic allergic alveolitis.
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-alpha, IL-1beta, 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- (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 6h was significantly suppressed by pretreatment 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.[1]References
- Effects of erythromycin on experimental extrinsic allergic alveolitis. Miyajima, M., Suga, M., Nakagawa, K., Ito, K., Ando, M. Clin. Exp. Allergy (1999) [Pubmed]
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