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.