1. Brown SMN1,2, Bush A1,2, Davies JC1,2, Thursfield R1,2, Lloyd CM1
The ratio IL-8:IL-10 is Increased in the Paediatric CF Airway as Compared to Other Neutrophilic Lung Diseases
Brown SMN1,2, Bush A1,2, Davies JC1,2, Thursfield R1,2, Lloyd CM1
1 National Heart & Lung Institute, Imperial College London UK, 2Royal Brompton Hospital London
Background
Cystic fibrosis (CF), bronchiectasis, primary ciliary dyskinesia (PCD) and persistent bacterial bronchitis (PBB) are characterised by persistent neutrophilic inflammation. One possible mechanism for the persistence of neutrophilic inflammation is failure of normal active resolution of the inflammatory process. Interleukin-10 (IL-10) is an anti-inflammatory cytokine. Studies in adults have reported lower IL-10 levels in the CF airway as compared to healthy controls, implying an impaired ability actively to resolve inflammation in the CF lung [1,2]. Children with CF tend to have less severe disease as compared to adults. It is possible that bronchoalveolar lavage (BAL) IL-10 is reduced in adults with more severe disease, but that children with milder disease have normal or raised levels in an attempt to control pulmonary inflammation. We hypothesised that the ability of IL-10 to resolve IL-8 mediated inflammation would be impaired in CF as compared to other neutrophilic lung diseases.
Patients & Methods
Children undergoing routine clinically indicated bronchoscopy were recruited. CF babies diagnosed on newborn screening (NBS) were also included as these babies routinely undergo bronchoscopy at 3 months of age. Control patients were those with isolated upper airway disease. BAL samples were stored at -80OC and cytokine levels analysed using a multiplex cytokine assay.
Results
BAL was obtained from 111 children (6 controls; 47 established CF; 19 CF NBS; 15 bronchiectasis; 6 PCD and 18 PBB. Bronchiectasis, PCD and PBB patients were grouped together as chronic suppurative lung disease (CSLD)). Data from BAL neutrophil counts is shown in graph A. BAL IL-10 levels were similar in controls and CF NBS subjects, but significantly higher in CF as compared to CF NBS (p<0.001) and controls (p<0.05). Levels were higher in CSLD as compared to
CF NBS (p<0.05) (Graph B). Given levels were similar in CF and CSLD, this was not related to the CFTR defect. On controlling for neutrophilic inflammation by expressing data as a ratio IL-10: BAL neutrophil count, no differences were observed between groups (Graph C). The ratio BAL IL-8: IL-10 was significantly higher in CF as compared to controls (p<0.05), CF NBS (p<0.001) and CSLD (p<0.0001) (Graph D). The ratio BAL IL-8: IL-10 was also higher in CF patients with positive BAL microbiological cultures as compared to those with no pathogens isolated at the time of bronchoscopy (p<0.001) (Graph E). The ratio IL-8: BAL neutrophils did not vary between groups.
Discussion
BAL IL-10 levels are elevated in paediatric neutrophilic lung disease irrespective of the underlying cause. Higher levels are seen in more severe neutrophilic disease. The ability of IL-10 to resolve IL-8 mediated inflammation appears to be impaired in CF as compared to other neutrophilic lung diseases and in children with CF with active infection. In addition this ability to resolve IL-8 mediated inflammation is impaired in established CF as compared to CF NBS, implying this is a phenomenon of those with more severe disease. Alternatively these findings may support the concept that IL-10 has both pro- and anti-inflammatory properties under certain circumstances [3]. The ratio of IL-8:BAL neutrophils did not vary between groups supporting the hypothesis that there are non-IL-8 pathways responsible for CF neutrophilic inflammation [4].
References
Am J Respir Cell Mol Biol 1995;13:
J Allergy Clin Immunol 1999;104:72-78)
Cytokine. 1998;10(11):
Thorax Jul;63(7):614-20
This project was supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London. The views expressed are those of the authors and not necessarily of the NHS, The National Institute of Health Research or the Department of Health.