Increased granulocyte macrophage-colony stimulating factor concentration in bronchoalveolar lavage fluid from patients with pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare disease that had been treated by whole-lung lavage. Recent reports of success in treating alveolar proteinosis with granulocyte macrophage-colony stimulating factor (GM-CSF) led us to the current study. We measured GM-CSF in the bronchoalveolar lavage (BAL) or whole-lung lavage fluid of five patients with PAP. GM-CSF levels were readily detectable in the BAL fluid. The GM-CSF levels in patients with PAP were similar to those in bacterial and Pneumocystis carinii pneumonia, but significantly higher than in healthy control subjects. Interleukin 8 and 10 concentrations were similar in the BAL fluid from patients with PAP or pneumonia. We studied the BAL fluid for autoantibodies to GM-CSF. In two of five patients, high levels of autoantibodies to GM-CSF were detected whereas GM-CSF autoantibodies were not detected in control subjects. We conclude that in these patients, the PAP was not related to defects in GM-CSF production, and that autoantibodies in the lung fluid may be blocking the effect of GM-CSF in the lung, contributing to the pathogenesis of PAP in some patients.