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Amoxicillin Modulates Leukosequestration and Proinflammatory Cytokine Release in Airway of Patients with Bronchiectasis

Amoxicillin調節支氣管擴張病人之呼吸道內白血球及前發炎細胞素之表現

摘要


Background: Bronchiectasis is a chronic airway disease of diverse etiology, characterized by persistent bacterial colonization, bronchial inflammation, and progressive tissue damage. Neutrophil influx with oxidants and pro-inflammatory cytokines production not only provides phagocytic protection from microbes, but is also implicated in further airway inflammation. This study was designed to investigate whether amoxicillin affects neutrophil-mediated airway inflammation in bronchiectasis. Methods: A 2-week course of therapy with amoxicillin (250mg, 4 times per day) or duracef (250mg, twice per day) was administered for bronchiectasis patients. Twenty-one bronchiectasis patients in stable condition after adequate chest care and hydration were enrolled in a randomized fashion. The neutrophil cellularity in 3 ml induced sputum was counted before and after treatment. The sputum IL-8 and TNF-α levels were measured using the ELISA method. Leukocyte adhesion molecules CD11b/CD18 and DCFH in induced sputum were determined by flow cytometric assay. Results: The total cell count of neutrophils in 3 ml induced sputum was significantly reduced in patients receiving amoxicillin from 14.4±5.1 to 9.3±5.2 (×10^6 cells) (p<0.05). There was no change in total cell counts in the duracef group (p=0.13). Amoxicillin significantly decreased the TNF-α and IL-8 levels in a supernatant of sputum, from 168.7±65.6pg/ml to 50.3±26.8pg/ml (p<0.01), and from 9538.4±1650.1pg/ml to 5664.4±1384.4pg/ml (p<0.01), respectively, whereas the TNF-α and IL-8 levels in the duracef group did not significantly change after treatment. In the amoxicillin group, the change in the sputum IL-8 level was significantly related to the change in the total cell count of leukocytes (r=0.67, n=11, p<0.05). There was also a significant correlation between the percentage of change in the sputum IL-8 level and total cell counts of leukocytes after antibiotic therapy in the amoxicillin group (r=0.76, n=11, p<0.01). The expression of CD11b, CD18 and DCFH did not significantly change after treatment in both groups. Conclusion: Different antibiotics have different effects on patients with bronchiectasis. Amoxicillin downregulates the TNF-α and IL-8 levels in sputum, thus leading to a decrease of airway neutrophil sequestration and preventing further airway damage.

並列摘要


Background: Bronchiectasis is a chronic airway disease of diverse etiology, characterized by persistent bacterial colonization, bronchial inflammation, and progressive tissue damage. Neutrophil influx with oxidants and pro-inflammatory cytokines production not only provides phagocytic protection from microbes, but is also implicated in further airway inflammation. This study was designed to investigate whether amoxicillin affects neutrophil-mediated airway inflammation in bronchiectasis. Methods: A 2-week course of therapy with amoxicillin (250mg, 4 times per day) or duracef (250mg, twice per day) was administered for bronchiectasis patients. Twenty-one bronchiectasis patients in stable condition after adequate chest care and hydration were enrolled in a randomized fashion. The neutrophil cellularity in 3 ml induced sputum was counted before and after treatment. The sputum IL-8 and TNF-α levels were measured using the ELISA method. Leukocyte adhesion molecules CD11b/CD18 and DCFH in induced sputum were determined by flow cytometric assay. Results: The total cell count of neutrophils in 3 ml induced sputum was significantly reduced in patients receiving amoxicillin from 14.4±5.1 to 9.3±5.2 (×10^6 cells) (p<0.05). There was no change in total cell counts in the duracef group (p=0.13). Amoxicillin significantly decreased the TNF-α and IL-8 levels in a supernatant of sputum, from 168.7±65.6pg/ml to 50.3±26.8pg/ml (p<0.01), and from 9538.4±1650.1pg/ml to 5664.4±1384.4pg/ml (p<0.01), respectively, whereas the TNF-α and IL-8 levels in the duracef group did not significantly change after treatment. In the amoxicillin group, the change in the sputum IL-8 level was significantly related to the change in the total cell count of leukocytes (r=0.67, n=11, p<0.05). There was also a significant correlation between the percentage of change in the sputum IL-8 level and total cell counts of leukocytes after antibiotic therapy in the amoxicillin group (r=0.76, n=11, p<0.01). The expression of CD11b, CD18 and DCFH did not significantly change after treatment in both groups. Conclusion: Different antibiotics have different effects on patients with bronchiectasis. Amoxicillin downregulates the TNF-α and IL-8 levels in sputum, thus leading to a decrease of airway neutrophil sequestration and preventing further airway damage.

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