title: Investigating the spill-over hypothesis: analysis of the association between local inflammatory markers in sputum and systemic inflammatory mediators in plasma.
abstract: Exposure to air pollutants represents a risk factor not only for respiratory diseases and lung cancer, but also for cardiometabolic diseases. It has been hypothesised that local inflammation in the lung and systemic subclinical inflammation are linked by impaired lung function and the spill-over of proinflammatory factors from the lung into the circulation which could act as intermediaries between environmental exposures and disease risk. We wanted to investigate whether local and systemic inflammatory markers are associated, which would support the spill-over hypothesis. Sputum and plasma samples were obtained from 257 women of the German SALIA cohort. We performed immunoassays to measure multiple biomarkers of airway inflammation in sputum as well as cytokines, chemokines and soluble adhesion molecules in plasma. Correlations were calculated and adjusted for potentially confounding variables. Even though several significant associations were detected between inflammatory mediators in sputum and plasma, correlation coefficients were rather low ranging from r≥-0.20 to r≤0.20. Comparatively stronger associations were observed between nitrite, eosinophil cationic protein, leukotrienes C/D/E4 and interleukin-8 in sputum. Notably, correlations were positive with all proinflammatory biomarkers and interleukin-1 receptor antagonist in plasma, whereas negative correlations were observed with the anti-inflammatory adipokine adiponectin. In conclusion, local inflammation in the lung and systemic subclinical inflammation appear mainly independently regulated in elderly women from the general population. Although we found multiple significant correlations between inflammatory biomarkers in sputum and plasma, our results do not provide clear support for the spill-over hypothesis.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 65, 40225 Düsseldorf, Germany. Electronic address: tom.teichert@ddz.uni-duesseldorf.de.
authors.forename: Tom
authors.initials: T
authors.lastname: Teichert
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 50, 40225 Düsseldorf, Germany. Electronic address: mohammad.vossoughi@iuf-duesseldorf.de.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Vossoughi
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 50, 40225 Düsseldorf, Germany. Electronic address: andrea.vierkoetter@iuf-duesseldorf.de.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vierkötter
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 50, 40225 Düsseldorf, Germany. Electronic address: dorothea.sugiri@iuf-duesseldorf.de.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Sugiri
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 50, 40225 Düsseldorf, Germany; Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland. Electronic address: tamara.schikowski@iuf-duesseldorf.de.
authors.forename: Tamara
authors.initials: T
authors.lastname: Schikowski
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 50, 40225 Düsseldorf, Germany; Medical Faculty, Heinrich Heine University of Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany. Electronic address: b.hoffmann@uni-duesseldorf.de.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hoffmann
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University Düsseldorf, Bergische Landstraße 2, 40629 Düsseldorf, Germany. Electronic address: thom.schulte@freenet.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schulte
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 65, 40225 Düsseldorf, Germany; Department of Endocrinology and Diabetology, University Hospital Düsseldorf, Heinrich Heine University, Universitätsstraße 1, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Auf׳m Hennekamp 65, 40225 Düsseldorf, Germany. Electronic address: michael.roden@ddz.uni-duesseldorf.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Center of Allergology/Immunology, Bürkle-de-la-Camp Platz 1, 44789 Bochum, Germany. Electronic address: raulf@ipa-dguv.de.
authors.forename: Monika
authors.initials: M
authors.lastname: Raulf-Heimsoth
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University Düsseldorf, Bergische Landstraße 2, 40629 Düsseldorf, Germany. Electronic address: christian.luckhaus@lvr.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Luckhaus
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 50, 40225 Düsseldorf, Germany. Electronic address: ursula.kraemer@iuf-duesseldorf.de.
authors.forename: Ursula
authors.initials: U
authors.lastname: Krämer
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf׳m Hennekamp 65, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Auf׳m Hennekamp 65, 40225 Düsseldorf, Germany. Electronic address: christian.herder@ddz.uni-duesseldorf.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D003430:Cross-Sectional Studies; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D013183:Sputum / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators
keywords: Airway inflammation; Cytokines; Induced sputum; Subclinical inflammation; Systemic inflammation