Neutrophil chemotactic activity in cryptogenic organizing pneumonia and the response to erythromycin

The present study was aimed at elucidating the role of inflammatory cells in the pathogenesis of cryptogenic organizing pneumonia, and the mode of action of erythromycin in inhibiting the progression of the disease. Bronchoalveolar lavage fluid was obtained from 16 patients with cryptogenic organizing pneumonia and 4 control subjects. Neutrophil chemotactic activity was determined in relation to the concentration of two cytokines, interleukin-8 and tumor necrosis factor-alpha. Eight patients with cryptogenic organizing pneumonia, 4 with bronchoalveolar lavage fluid neutrophilia and 4 without, received low dose oral erythromycin daily (600 mg) for 2 to 3 months. Bronchoalveolar lavage fluid was obtained before and after treatment. In the bronchoalveolar lavage fluid of cryptogenic organizing pneumonia patients with bronchoalveolar lavage fluid neutrophilia, the levels of neutrophil chemotactic activity, interleukin-8, and tumor necrosis factor-alpha were significantly increased compared with levels measured in control subjects and in cryptogenic organizing pneumonia patients without bronchoalveolar lavage fluid neutrophilia. The level of interleukin-8 correlated with the percent of neutrophils and neutrophil chemotactic activity of bronchoalveolar lavage fluid, while the level of tumor necrosis factor-alpha did not. Furthermore, the levels of interleukin-8 and neutrophil chemotactic activity in the bronchoalveolar lavage fluid of cryptogenic organizing pneumonia patients with bronchoalveolar lavage fluid neutrophilia were significantly decreased following treatment with erythromycin. In contrast, the level of tumor necrosis factor-alpha was not affected by treatment with erythromycin. It is possible that cryptogenic organizing pneumonia is caused by neutrophil-mediated inflammation, and that the favorable clinical effect of erythromycin is due to inhibition of neutrophil accumulation in the peripheral airways through a biological activity other than bacteriostasis, e.g., local suppression of interleukin-8 production.