Neutrophilic Inflammation and CXC Chemokines in Patients with Refractory Asthma

Abstract

Background: There is evidence that eosinophils and neutrophils are simultaneously increased in the airways of some patients with chronic refractory asthma. The mechanisms by which neutrophils accumulate in the airways of asthmatics remain to be elucidated, however, chemoattractants for neutrophils such as CXC chemokines may affect either the accumulation or functional status of neutrophils in such patients. The objective of the present study was to identify the CXC chemokine responsible for the neutrophilic and possibly eosinophilic inflammation observed in the airways of patients with refractory asthma. Methods: Following the inhalation of hypertonic saline, induced sputum was obtained from 14 healthy controls, 16 patients with mild well-controlled nonrefractory asthma, and 14 patients with refractory asthma. Concentrations of CXC chemokines and differential inflammatory cell counts were determined. Results: The percentages of induced sputum eosinophils were significantly higher both in patients with nonrefractory asthma and in patients with refractory asthma. On the other hand, the percentages of neutrophils were increased only in sputum from patients with refractory asthma. The concentration of IL-8, but not ENA-78 or GRO-α, was also significantly increased in induced sputum from patients with refractory asthma. The concentration of IL-8 correlated significantly with the percentages of neutrophils. Conclusions: The results of the present study suggest that IL-8, but not ENA-78 or GRO-α, may contribute to the observation of neutrophilic inflammation in patients with refractory asthma.