Dataset Information

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.

SUBMITTER: Andelid K

PROVIDER: S-EPMC4381892 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Systemic cytokine signaling via IL-17 in smokers with obstructive pulmonary disease: a link to bacterial colonization?

Andelid Kristina K Tengvall Sara S Andersson Anders A Levänen Bettina B Christenson Karin K Jirholt Pernilla P Åhrén Christina C Qvarfordt Ingemar I Ekberg-Jansson Ann A Lindén Anders A

International journal of chronic obstructive pulmonary disease 20150327

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 ...[more]

PMID: 25848245

Similar Datasets

Project description:Pseudomonas aeruginosa airway infection increases risks of exacerbations and mortality in chronic obstructive pulmonary disease (COPD). We aimed to elucidate the role of IL-17 in the pathogenesis. We examined the expression and influences of IL-23/IL-17A in patients with stable COPD (n = 33) or acute COPD exacerbations with P. aeruginosa infection (n = 34). A mouse model of COPD (C57BL/6) was used to investigate the role of IL-17A in host inflammatory responses against P. aeruginosa infection through the application of IL-17A-neutralizing antibody or recombinant IL-17A. We found that P. aeruginosa infection increased IL-23/17A signaling in lungs of both COPD patients and COPD mouse models. When COPD mouse models were treated with neutralizing antibody targeting IL-17A, P. aeruginosa induced a significantly less polymorphonuclear leukocyte infiltration and less bacterial burden in their lungs compared to those of untreated counterparts. The lung function was also improved by neutralizing antibody. Furthermore, IL-17A-signaling blockade significantly reduced the expression of pro-inflammatory cytokine IL-1β, IL-18, TNF-α, CXCL1, CXCL15 and MMP-9, and increased the expression of anti-inflammatory cytokine IL-10 and IL-1Ra. The application of mouse recombinant IL-17A exacerbated P. aeruginosa-mediated inflammatory responses and pulmonary dysfunction in COPD mouse models. A cytokine protein array revealed that the expression of retinol binding protein 4 (RBP4) was down-regulated by IL-17A, and exogenous RBP4-recombinant protein resulted in a decrease in the severity of P. aeruginosa-induced airway dysfunction. Concurrent application of IL-17A-neutralizing antibody and ciprofloxacin attenuated airway inflammation and ventilation after inoculation of P. aeruginosa in COPD mouse models. Our results revealed that IL-17 plays a detrimental role in the pathogenesis of P. aeruginosa airway infection during acute exacerbations of COPD. Targeting IL-17A is a potential therapeutic strategy in controlling the outcomes of P. aeruginosa infection in COPD patients.

Project description:RationaleSleep disturbance frequently affects patients with chronic obstructive pulmonary disease (COPD), and is associated with reduced quality of life and poorer outcomes. Data indicate that smokers with preserved pulmonary function have clinical symptoms similar to those meeting spirometric criteria for COPD, but little is known about the driving factors for sleep disturbance in this population of emerging interest.ObjectivesTo compare the magnitude and correlates of sleep disturbance between smokers with preserved pulmonary function and those with airflow obstruction.MethodsUsing cross-sectional data from the COPD Outcomes-Based Network for Clinical Effectiveness and Research Translation multicenter registry, we identified participants clinically identified as having COPD with a smoking history of at least 20 pack-years and either preserved pulmonary function or airflow obstruction. We quantified sleep disturbance by T-score measured in the sleep disturbance domain of the Patient-Reported Outcomes Information System questionnaire, and defined a minimum important difference as a T-score difference of two points. We performed univariate and multivariable linear regression to evaluate correlates within each group.ResultsWe identified 100 smokers with preserved pulmonary function and 476 with airflow obstruction. The sleep disturbance T-score was 4.1 points greater among individuals with preserved pulmonary function (95% confidence interval [CI], 2.0-6.3). In adjusted analyses, depression symptom T-score was associated with sleep disturbance in both groups (airflow obstruction: β, 0.61 points; 95% CI, 0.27-0.94; preserved pulmonary function: β, 0.25 points; 95% CI, 0.12-0.38). Of note, lower percent predicted FEV1 was associated with greater sleep disturbance among those with preserved pulmonary function (β, -0.19 points; 95% CI, -0.31 to -0.07), whereas higher FEV1 was associated with greater sleep disturbance among individuals with airflow obstruction (β, 0.06 points; 95% CI, 0.01-0.10).ConclusionsAmong smokers with clinically identified COPD, the severity of sleep disturbance is greater among those with preserved pulmonary function compared with those with airflow obstruction. Nonrespiratory symptoms, such as depression, were associated with sleep disturbance in both groups, whereas the relationship of sleep disturbance with FEV1 differed.

Project description:BackgroundWe organized this study in order to investigate differences in serum inflammatory profiles and circulating serum pneumoproteins between smokers with and without chronic obstructive pulmonary disease (COPD).MethodsPatients aged 35-70 years with COPD and a smoking history ≥10 pack-years (cases, n=38) and 38 participants with the same smoking history without COPD (controls) were included in a comparative study conducted as part of a population-based cross-sectional study with 2,388 individuals in northwestern Russia. Cases and controls were matched for age and smoking history. Airflow obstruction (AO) was defined using forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <0.70 and/or FEV1/FVC < lower limit of the normal cut-off values. Patients at risk for COPD were reassessed using a standardized diagnostic work-up protocol. Several parameters, among which four inflammatory biomarkers [the high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) levels] and two pneumoproteins [surfactant protein D (SP-D) and Clara cell secretory protein 16 (CC16)], were measured in the peripheral blood. Systemic inflammation was defined as at least 2 or more elevated biomarker levels.ResultsOut of all smokers, 57.9% with normal spirometry and 36.8% with COPD did not have systemic inflammation, whereas 44.7% of the patients with COPD and 5.3% of the patients without AO demonstrated at least two elevated biomarker levels. No difference in age, gender, and smoking history, environmental and occupational exposure was found between the non-inflamed and the inflamed smokers. Of all risk factors studied, only COPD was associated with systemic inflammation [odds ratio (OR) 11.42, 95% confidence interval (CI): 2.13-58.84].ConclusionsOur study describes the systemic inflammatory network pattern associated with COPD and how it differs from the pattern in smokers with normal lung function. Systemic inflammation is not present in all smokers with COPD; in contrast, some non-obstructed smokers are characterized by systemic inflammation. From this perspective, smoking itself could be seen as a disease and studied accordingly.Trial registrationNCT02307799.

Dataset Information

Systemic cytokine signaling via IL-17 in smokers with obstructive pulmonary disease: a link to bacterial colonization?

Publications

Systemic cytokine signaling via IL-17 in smokers with obstructive pulmonary disease: a link to bacterial colonization?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets