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Effects of erythromycin on experimental extrinsic allergic alveolitis.

AbstractBACKGROUND:
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.
AuthorsM Miyajima, M Suga, K Nakagawa, K Ito, M Ando
JournalClinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 29 Issue 2 Pg. 253-61 (Feb 1999) ISSN: 0954-7894 [Print] England
PMID10051731 (Publication Type: Journal Article)
Chemical References
  • Anti-Bacterial Agents
  • Ccl9 protein, mouse
  • Chemokines, CC
  • Cytokines
  • Macrophage Inflammatory Proteins
  • Intercellular Adhesion Molecule-1
  • Erythromycin
  • Peroxidase
Topics
  • Alveolitis, Extrinsic Allergic (drug therapy, metabolism, microbiology)
  • Animals
  • Anti-Bacterial Agents (therapeutic use)
  • Arthus Reaction (prevention & control)
  • Bronchoalveolar Lavage Fluid
  • Chemokines, CC
  • Chemotaxis, Leukocyte (drug effects)
  • Cytokines (metabolism)
  • Disease Models, Animal
  • Erythromycin (therapeutic use)
  • Female
  • Immunoenzyme Techniques
  • Intercellular Adhesion Molecule-1 (metabolism)
  • Lung (drug effects, metabolism, pathology)
  • Macrophage Inflammatory Proteins
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils (drug effects)
  • Peroxidase (metabolism)
  • Specific Pathogen-Free Organisms
  • Trichosporon

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