Effects of erythromycin on experimental extrinsic allergic alveolitis

• Published in: Clinical and experimental allergy Vol. 29; no. 2; pp. 253 - 261
• Main Authors: MIYAJIMA, M, SUGA, M, NAKAGAWA, K, ITO, K, ANDO, M
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.02.1999; Blackwell; Wiley Subscription Services, Inc
• Subjects: Alveolitis, Extrinsic Allergic - drug therapy; Alveolitis, Extrinsic Allergic - metabolism; Alveolitis, Extrinsic Allergic - microbiology; animal model; Animals; Anti-Bacterial Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Arthus reaction; Arthus Reaction - prevention & control; Biological and medical sciences; Bronchoalveolar Lavage Fluid; Chemokines, CC; Chemotaxis, Leukocyte - drug effects; Cytokines - metabolism; Disease Models, Animal; erythromycin; Erythromycin - therapeutic use; extrinsic allergic alveolitis; Female; hypersensitivity pneumonitis; Immunoenzyme Techniques; intercellular adhesion molecule-1 (ICAM-1); Intercellular Adhesion Molecule-1 - metabolism; Lung - drug effects; Lung - metabolism; Lung - pathology; Macrophage Inflammatory Proteins; Medical sciences; Mice; Mice, Inbred C57BL; Miscellaneous. Antibiotics with multiple activities; Neutrophils - drug effects; Peroxidase - metabolism; Pharmacology. Drug treatments; Specific Pathogen-Free Organisms; summer-type hypersensitivity pneumonitis; Trichosporon; Trichosporon mucoides; Immunopathology; Lung disease; Allergy; Animal model; Arthus phenomenon(reaction); Intercellular adhesion molecule 1; Respiratory disease; Rodentia; Antiinflammatory agent; Erythromycin; Macrolide; Biological activity; Vertebrata; Antibiotic; Chemotherapy; Mammalia; Treatment; Mouse; Animal; Interstitial pneumonitis; Antibacterial agent; Mechanism of action
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1046/j.1365-2222.1999.00430.x

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.