Circadian changes in granulocyte-macrophage colony-stimulating factor message in circulating eosinophils

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF), which stimulates eosinophil recruitment, activation, and survival, is expressed by activated eosinophils. Although eosinophil recruitment and enhanced survival have been associated with nocturnal asthma (NA), the contribution of GM-CSF to NA is unknown. To determine whether circulating eosinophil GM-CSF expression correlates with the symptoms of NA. The GM-CSF messenger RNA (mRNA) expression at 4 PM and 4 AM was determined by reverse-transcriptase polymerase chain reaction with Southern blot analysis in subjects with and without NA and in controls. A total of 142 asthma subjects were screened for nocturnal asthma with 1-week home peak expiratory flow rate (PEFR) monitoring. Eleven subjects had NA (>20% diurnal variation in PEFR on 4 of 7 days), and 6 met the criteria for non-NA (<10% diurnal variation in PEFR on 7 of 7 days); 8 controls were studied. In subjects with NA, GM-CSF mRNA expression in circulating eosinophils increased 3-fold at 4 AM compared with 4 PM. Diurnal changes in GM-CSF mRNA expression were not detected in the non-NA and control groups. Day-night variation in eosinophil GM-CSF expression is associated with circadian variation in airway function in asthma, a key manifestation of asthma severity.