Non-antibiotic effect of antibiotics.

In the present study, we demonstrated the efficacy of low-dose, long-term therapy with erythromycin and an erythromycin-related compound, roxithromycin, in patients with chronic lower respiratory tract disease including diffuse panbronchiolitis (DPB), and investigated the anti-inflammatory action of such drugs. Treatment significantly improved the mean value of respiratory function tests and arterial blood gas analysis, except for PaCO2 in the erythromycin-treated group and residual volume/total lung capacity (RV/TLC) and PaCO2 in the roxithromycin-treated group. Bronchoalveolar lavage (BAL) analysis revealed that neutrophils had accumulated in the pre-treatment lavage fluid, compared with that of healthy volunteers, and the levels of neutrophil chemotactic activity (NCA), interleukin-1beta (IL-1beta), interleukin-8 (IL-8) and leukotriene B4 (LTB4) in BAL fluid of the patients were significantly higher than those in healthy volunteers. Macrolide therapy caused a significant reduction in the percentage of neutrophils, NCA and mean IL-1beta, IL-8 and LTB4 concentration in BAL fluid of the patients. The quantitative expression of Mac---1 on peripheral neutrophils significantly increased, compared with that in healthy volunteers, before therapy and significantly decreased after therapy. We also evaluated the in vitro inhibitory effects of macrolides on IL---8 production by vitamin D3-induced human monocytic cell line THP-1 cells when stimulated with lipopolysaccharide and serum. The present study has also provided evidence for T-cell activation in BAL fluid of the patients, and a significantly reduced number of activated T-cells was observed after macrolide therapy. These results indicate that macrolides may act by reducing pulmonary inflammation through reduction of neutrophil accumulation, as a consequence of reduced chemotactic gradient and cytokine production at the inflammatory sites in the lung or of reduced neutrophil adhesion molecules in the circulation. Ultimately the mechanism may involve suppression of neutrophil oxidative and proteolytic products. Lymphocytes are important cellular components of bronchial inflammation, in addition to neutrophils, in this disease, and macrolide antibiotics may also act as an immunosuppressant to inhibit T-cell activation. This is believed to be one reason why macrolides are effective in chronic lower respiratory tract disease.