Macrolide antibiotics induce apoptosis of human peripheral lymphocytes in vitro.

We previously reported that long-term administration of macrolides (MCL) reduced the number of lymphocytes in bronchoalveolar lavage fluid (BALF) of patients with chronic lower respiratory tract disease. To investigate the anti-inflammatory activity of macrolides, we evaluated their effect on apoptosis of lymphocytes isolated from human peripheral blood. Lymphocytes treated with clarithromycin, azithromycin and josamycin at a final concentration of 200 microg/ml showed positive staining for Annexin V, Fas and Fas ligand using flow cytometry with time at 12-72 h, while other antibiotics did not. Our results suggest that macrolides induce apoptosis of lymphocytes through Fas-Fas ligand pathway and could potentially reduce the number of lymphocytes in the lungs of patients with chronic lower respiratory tract disease.

High concentrations of soluble Fas ligand in bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis.

BACKGROUND AND OBJECTIVES: Sarcoidosis is a systematic granulomatous disorder of unknown origin characterized by accumulation of T lymphocytes and macrophages in multiple organs. We postulated that apoptosis through the Fas/Fas ligand (L) system may be associated with regulation of immune reactions characterized by the formation of noncaseous necrotizing granulomas. Soluble (s) FasL is not equivalent to membrane-associated FasL since conversion of membrane-bound FasL to the soluble form is associated with downregulation of cytotoxicity. To examine the involvement of sFasL in lung inflammation, we compared the levels of sFasL in bronchoalveolar lavage (BAL) fluid and serum of patients with pulmonary sarcoidosis to those of healthy subjects. METHODS: sFasL was measured in BAL fluid and in serum of 15 patients with active pulmonary sarcoidosis by sandwich ELISA. RESULTS: High concentrations of sFasL were detected in BAL fluid and serum of patients with sarcoidosis but not in normal subjects. There was a significant correlation between the percentage of lymphocytes and sFasL concentrations in BAL fluid (r = 0.585, p < 0.05). CONCLUSIONS: Our results suggest that sFasL may be upregulated locally in the lung during the inflammatory process of active pulmonary sarcoidosis.