Distinct sputum cytokine profiles in cystic fibrosis and other chronic inflammatory airway disease

Abstract

The dominant role of inflammation in airways disease progression in cystic fibrosis (CF) is now well established and, based on recent findings, the possibility of an inappropriate inflammatory response in the lung of patients with CF has emerged. In order to characterize this response, the aim of the present work was to evaluate the levels of a number of pro- and anti-inflammatory cytokines in the sputum of CF children and to compare these levels to those observed in the sputum from non-CF children with diffuse bronchiectasis (DB). Three groups of patients were investigated: a group of 25 CF children (mean age: 12.2 yrs), a group of 10 non-CF children with DB (mean age 11.5 yrs), and a group of five healthy young adults (mean age 24 yrs). Elevated concentrations of pro-inflammatory cytokines, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-8 were found in children with CF and in non-CF children with DB, with significantly higher concentrations of IL-1beta in CF children. Analysis of the natural anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) and type II TNF soluble receptor (sTNFRII) concentrations showed distinct patterns, with elevated levels of both inhibitors in CF patients, whereas only sTNFRII was found to be increased in non-CF children with DB. IL-10 data indicated low concentrations in the CF group. In all CF children, the concentrations of IL-6 in the airways were extremely low, independent of the clinical, bacteriological or functional status. By contrast, significantly increased IL-6 levels were found in non-CF children with DB. These results document distinct cytokine profiles in cystic fibrosis patients and noncystic fibrosis patients. They also suggest that impairment of interleukin-6 expression may represent an important component of the excessive inflammatory response observed in cystic fibrosis.