Systemic and exhaled cytokine and chemokine profiles are associated with the development of bronchiolitis obliterans syndrome

Background

The mechanisms that lead to the fibrotic obliteration in bronchiolitis obliterans syndrome (BOS) may involve the interactions between T-helper (Th)1 and Th2 cytokines. The aim of this study is to determine the Th1 and Th2 cytokine and chemokine profiles in serum and exhaled breath condensate (EBC) in lung transplant recipients and to assess their usefulness as biomarkers to predict the development of BOS.

Methods

Serum and EBC from 10 patients with BOS (BOS^pos) and 10 patients without BOS (BOS^neg), matched for clinical and demographic variables, were analyzed with a multiplex immunoassay to measure a panel of 27 cytokines and chemokines.

Results

The pro-inflammatory cytokines in serum were elevated in lung transplant recipients compared with controls. BOS^pos patients had significantly lower concentrations of interleukin (IL)-4, IL-13, and vascular endothelial growth factor (VEGF) compared with BOS^neg patients. The concentration of IL-5, however, was significantly higher in BOS^pos patients. Levels of IL-4 and IL-5 were hardly detectable in EBC. IL-13 and VEGF, both decreased in serum in BOS^pos patients, were also decreased in EBC in BOS^pos patients compared with BOS^neg patients. Longitudinal analysis of cytokines and chemokines in serum and EBC from the time of lung transplantation onwards did not reveal significant trends in cytokines and chemokines that preceded the diagnosis of BOS.

Conclusions

Levels of pro-inflammatory cytokines were increased in lung transplant recipients compared with controls. From the moment of transplantation onwards, there is a different pattern of Th2 cytokines in serum in BOS^pos patients than in BOS^neg patients.

Keywords: cytokines, chemokines, serum, lung transplantation, BOS