CYTOKINES IN BRONCHOALVEOLAR LAVAGE FLUID OF PATIENTS WITH NOCTURNAL ASTHMA

Airflow obstruction can have a circadian pattern with nocturnal worsening. Airway inflammation is a cardinal feature of asthma, and it has been shown to increase at night in association with the decline in pulmonary function. Although the mechanisms regulating enhanced airway inflammation in asthma at night have yet to be ascertained, we hypothesized that circadian variation in cytokine expression or production is an important factor in the development of nocturnal airflow limitation. To investigate this possibility, spirometry and bronchoscopy were performed; the bronchoalveolar ravage (BAL) fluid obtained at 4:00 A.M. and at 4:00 P.M. were measured for IL-1(beta) in asthmatics with (n = 5) and without (n = 9) nocturnal asthma. In addition, the activity of IL-3, IL-5, and CM-CSF was measured using a biologic assay (eosinophil survival-enhancing activity). BAL fluid concentrations of IL-1(beta) were significantly greater at 4:00 A.M. than at 4:00 P.M. (1.14 +/- 0.6 versus 0.7 +/- 0.6 pg/ml; p = 0.05) in asthmatics with nocturnal airflow obstruction. Moreover, Il-(1 beta) levels at 4:00 A.M. tended to be higher in subjects with nocturnal asthma than in those without nighttime airflow reduction (1.14 +/- 0.6 versus 0.3 +/- 0.4 pg/m I; p = 0.1). On the other hand, eosinophil survival-enhancing activity in BAL fluid, which is usually associated with IL-3, IL-5, or GM-CSF, was not detected in relationship to nocturnal asthma. Because IL-1(beta) can activate air-space cells, particularly alveolar macrophages, we propose that an increased release of this cytokine is a significant contributor to nocturnal airway inflammation and obstruction in asthma.