Effects of erythromycin on experimental extrinsic allergic alveolitis

Clin Exp Allergy. 1999 Feb;29(2):253-61. 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-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.

MeSH terms

  • Alveolitis, Extrinsic Allergic / drug therapy*
  • Alveolitis, Extrinsic Allergic / metabolism
  • Alveolitis, Extrinsic Allergic / 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*
  • Lung / metabolism
  • Lung / pathology
  • Macrophage Inflammatory Proteins*
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / drug effects
  • Peroxidase / metabolism
  • Specific Pathogen-Free Organisms
  • Trichosporon


  • Anti-Bacterial Agents
  • Ccl9 protein, mouse
  • Chemokines, CC
  • Cytokines
  • Macrophage Inflammatory Proteins
  • Intercellular Adhesion Molecule-1
  • Erythromycin
  • Peroxidase