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: 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.
|
Authors | M Miyajima, M Suga, K Nakagawa, K Ito, M Ando |
Journal | Clinical 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 |
PMID | 10051731
(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
|