title: Systemic cytokine signaling via IL-17 in smokers with obstructive pulmonary disease: a link to bacterial colonization?
abstract: We examined whether systemic cytokine signaling via interleukin (IL)-17 and growth-related oncogene-α (GRO-α) is impaired in smokers with obstructive pulmonary disease including chronic bronchitis (OPD-CB). We also examined how this systemic cytokine signaling relates to bacterial colonization in the airways of the smokers with OPD-CB. Currently smoking OPD-CB patients (n=60, corresponding to Global initiative for chronic Obstructive Lung Disease [GOLD] stage I-IV) underwent recurrent blood and sputum sampling over 60 weeks, during stable conditions and at exacerbations. We characterized cytokine protein concentrations in blood and bacterial growth in sputum. Asymptomatic smokers (n=10) and never-smokers (n=10) were included as control groups. During stable clinical conditions, the protein concentrations of IL-17 and GRO-α were markedly lower among OPD-CB patients compared with never-smoker controls, whereas the asymptomatic smoker controls displayed intermediate concentrations. Notably, among OPD-CB patients, colonization by opportunistic pathogens was associated with markedly lower IL-17 and GRO-α, compared with colonization by common respiratory pathogens or oropharyngeal flora. During exacerbations in the OPD-CB patients, GRO-α and neutrophil concentrations were increased, whereas protein concentrations and messenger RNA for IL-17 were not detectable in a reproducible manner. In smokers with OPD-CB, systemic cytokine signaling via IL-17 and GRO-α is impaired and this alteration may be linked to colonization by opportunistic pathogens in the airways. Given the potential pathogenic and therapeutic implications, these findings deserve to be validated in new and larger patient cohorts.
authors.affiliation: Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Andelid
authors.affiliation: Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Tengvall
authors.affiliation: Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Andersson
authors.affiliation: Unit of Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bettina
authors.initials: B
authors.lastname: Levänen
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Christenson
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Jirholt
authors.affiliation: Department of Infectious Diseases, Infection Control Unit, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Åhrén
authors.affiliation: Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ingemar
authors.initials: I
authors.lastname: Qvarfordt
authors.affiliation: Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ann
authors.initials: A
authors.lastname: Ekberg-Jansson
authors.affiliation: Unit of Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Lindén
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D054360:Chemokine CXCL1 / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D020381:Interleukin-17 / Q000097:blood*; D008137:Longitudinal Studies; D008168:Lung / Q000276:immunology / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology; D009894:Opportunistic Infections / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology; D011014:Pneumonia / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology; D012907:Smoking / Q000009:adverse effects / Q000097:blood* / Q000276:immunology; D013183:Sputum / Q000382:microbiology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D018836:Inflammation Mediators; D020381:Interleukin-17; D002097:C-Reactive Protein
keywords: COPD; exacerbation; infection; lung; neutrophil; opportunist
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