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

Andelid, Kristina; Tengvall, Sara; Andersson, Anders; Levänen, Bettina; Christenson, Karin; Jirholt, Pernilla; Åhrén, Christina; Qvarfordt, Ingemar; Ekberg-Jansson, Ann; Lindén, Anders

doi:10.2147/copd.s76273

Cited by 13 publications

(22 citation statements)

References 29 publications

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“…While direct comparisons are not yet available, the pattern of changes we observed upon exposure to PM 2.5 seems to differ from that observed with smoking. Although like PM 2.5 exposure, smoking is also associated with endothelial apoptosis and a decrease in plasma levels of CD40L, 59 EGF, 60 and GROα 61 it is generally associated with increased blood levels of VEGF, 62 which due to stimulatory effect of nicotine on VEGF 63 or because of hypoxia induced by CO in cigarette smoke. Also, unlike PM 2.5 exposure, smoking is not usually associated with an increase in plasma TNFα or MCP-1 levels.…”

Section: Discussionmentioning

confidence: 99%

Exposure to Fine Particulate Air Pollution Is Associated With Endothelial Injury and Systemic Inflammation

Pope

Bhatnagar

McCracken

et al. 2016

Circulation Research

499

278

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Rationale Epidemiologic evidence indicates that exposures to fine particulate matter air pollution (PM2.5) contribute to global burden of disease, primarily as a result of increased risk of cardiovascular morbidity and mortality. However, mechanisms by which PM2.5 exposure induces cardiovascular injury remain unclear. PM2.5-induced endothelial dysfunction and systemic inflammation have been implicated, but direct evidence is lacking. Objective To examine whether acute exposure to PM2.5 is associated with endothelial injury and systemic inflammation. Methods and Results Blood was collected from healthy, non-smoking, young adults over three study periods that included episodes of elevated PM2.5 levels. Microparticles and immune cells in blood were measured by flow cytometry, and plasma cytokine/growth factors were measured using multiplexing laser beads. PM2.5 exposure was associated with elevated levels of endothelial microparticles (annexin V+/CD41−/CD31+) including subtypes expressing arterial-, venous-, and lung-specific markers, but not microparticles expressing CD62+. These changes were accompanied by suppressed circulating levels of pro-angiogenic growth factors (EGF, sCD40L, PDGF, RANTES, GROα, and VEGF), and an increase in the levels of anti-angiogenic (TNFα, IP-10) and proinflammatory cytokines (MCP-1, MIP-1α/β, IL-6, and IL-1β), and markers of endothelial adhesion (sICAM-1 and sVCAM-1). PM2.5 exposure also was associated with an inflammatory response characterized by elevated levels of circulating CD14+, CD16+, CD4+, and CD8+, but not CD19+ cells. Conclusions Episodic PM2.5 exposures are associated with increased endothelial cell apoptosis, an anti-angiogenic plasma profile, and elevated levels of circulating monocytes, and T, but not B, lymphocytes. These changes could contribute to the pathogenic sequelae of atherogenesis and acute coronary events.

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Section: Discussionmentioning

confidence: 99%

Exposure to Fine Particulate Air Pollution Is Associated With Endothelial Injury and Systemic Inflammation

Pope

Bhatnagar

McCracken

et al. 2016

Circulation Research

499

278

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“…Hypothetically, our data showing a decline in the content of IL-17 in BAL CD4+ T cells from smokers illustrate a feasible mechanistic explanation for bacterial colonization and increased susceptibility to infection in the lungs of smokers [26]. Interestingly, it was recently shown that in smokers with obstructive pulmonary disease including chronic bronchitis, lower systemic levels of IL-17 was associated with colonization by opportunistic pathogens in the airways [27]. The negative effect of smoking on adaptive immune responses in animal studies has been reported before [28].…”

Section: Discussionmentioning

confidence: 75%

Distinctive Regulatory T Cells and Altered Cytokine Profile Locally in the Airways of Young Smokers with Normal Lung Function

et al. 2016

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Smoking influences the immune system in different ways and, hypothetically, effects on pulmonary effector and regulatory T cells emerge as potentially detrimental. Therefore, we characterized the frequencies and characteristics of CD4+ and CD8+ T cell subsets in the blood and lungs of young tobacco smokers. Bronchoalveolar lavage (BAL) and peripheral blood were obtained from healthy moderate smokers (n = 18; 2–24 pack-years) and never-smokers (n = 15), all with normal lung function. Cells were stimulated ex vivo and key intracellular cytokines (IFNγ, IL-17, IL-10 and TNFα) and transcription factors (Foxp3, T-bet and Helios) were analyzed using flow cytometry. Our results indicate that smoking is associated with a decline in lung IL-17+ CD4+ T cells, increased IFNγ+ CD8+ T cells and these alterations relate to the history of daily cigarette consumption. There is an increased fraction of Foxp3+ regulatory T cells being Helios- in the lungs of smokers. Cytokine production is mainly confined to the Helios- T cells, both in regulatory and effector subsets. Moreover, we detected a decline of Helios+Foxp3- postulated regulatory CD8+ T cells in smokers. These alterations in the immune system are likely to increase risk for infection and may have implications for autoimmune processes initiated in the lungs among tobacco smokers.

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“…The clinical characteristics of the study subjects during clinically stable periods at the time of inclusion are published elsewhere. 20 Briefly, smokers with OPD-CB of any Global Initiative for Chronic Obstructive Lung Disease stage were included, with only slight differences in age between the groups. Although we aimed to recruit equal numbers of men and women, there was a predominance of women in all study groups, and the tobacco load was somewhat higher in the group of smokers with OPD-CB than in the AS group.…”

Section: Resultsmentioning

confidence: 99%

“…Although we aimed to recruit equal numbers of men and women, there was a predominance of women in all study groups, and the tobacco load was somewhat higher in the group of smokers with OPD-CB than in the AS group. 20 …”

Section: Resultsmentioning

confidence: 99%

“…The results of sputum culture during clinically stable periods at the time of inclusion have been published elsewhere. 20 Briefly, sputum samples for culture of bacteria were obtained from 87% of the smokers with OPD-CB at the time of inclusion, generating 40 samples that were representative of the peripheral airways. Seventeen of these representative samples grew common respiratory pathogens (mainly Haemophilus influenzae ), three grew opportunistic pathogens, and 20 grew oropharyngeal flora.…”

Section: Resultsmentioning

confidence: 99%

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Systemic signs of neutrophil mobilization during clinically stable periods and during exacerbations in smokers with obstructive pulmonary disease

Andelid¹,

Andersson²,

Yoshihara³

et al. 2015

COPD

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BackgroundIt is still unclear whether signs of neutrophil mobilization in the blood of patients with chronic obstructive pulmonary disease represent true systemic events and how these relate to bacterial colonization in the airways. In this study, we evaluated these issues during clinically stable periods and during exacerbations in smokers with obstructive pulmonary disease and chronic bronchitis (OPD-CB).MethodsOver a period of 60 weeks for each subject, blood samples were repeatedly collected from 60 smokers with OPD-CB during clinically stable periods, as well as during and after exacerbations. Myeloperoxidase (MPO) and neutrophil elastase (NE) protein and mRNA, growth of bacteria in sputum, and clinical parameters were analyzed. Ten asymptomatic smokers and ten never-smokers were included as controls.ResultsWe found that, during clinically stable periods, neutrophil and NE protein concentrations were increased in smokers with OPD-CB and in the asymptomatic smokers when compared with never-smokers. During exacerbations, neutrophil and MPO protein concentrations were further increased in smokers with OPD-CB, without a detectable increase in the corresponding mRNA during exacerbations. However, MPO and NE protein and mRNA displayed positive correlations. During exacerbations, only increased neutrophil concentrations were associated with growth of bacteria in sputum. Among patients with low transcutaneous oxygen saturation during exacerbations, PaO2 (partial oxygen pressure) correlated with concentrations of MPO and NE protein and neutrophils in a negative manner.ConclusionThere are signs of systemic neutrophil mobilization during clinically stable periods and even more so during exacerbations in chronic obstructive pulmonary disease. In this condition, MPO and NE may share a cellular origin, but its location remains uncertain. Factors other than local bacteria, including hypoxemia, may be important for driving systemic signs of neutrophil mobilization.

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

Cited by 13 publications

References 29 publications

Exposure to Fine Particulate Air Pollution Is Associated With Endothelial Injury and Systemic Inflammation

Exposure to Fine Particulate Air Pollution Is Associated With Endothelial Injury and Systemic Inflammation

Distinctive Regulatory T Cells and Altered Cytokine Profile Locally in the Airways of Young Smokers with Normal Lung Function

Systemic signs of neutrophil mobilization during clinically stable periods and during exacerbations in smokers with obstructive pulmonary disease

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