IL-6, a central acute-phase mediator, as an early biomarker for exposure to zinc-based metal fumes.
OBJECTIVE
Systemic C-reactive protein (CRP) increases 1day after short-term inhalation of welding fumes containing zinc and/or copper. The aim of the current study was to find further, possibly earlier systemic biomarkers after inhalation of different welding fumes containing zinc and traces of aluminum, with or without copper, as these metal combinations become more common in modern joining technology.


METHODS
The study group consisted of 15 non-smoking male volunteers with healthy lung function data and without any occupational metal fume exposure. On 4 different exposure days, the members of the study group were exposed under controlled conditions to ambient air or 3 different welding fumes for 6h. Spirometric and impulse oscillometric measurements and differential blood counts were performed and serum samples were collected before exposure and 6, 10 and 29h after start of exposure. The biomarker concentrations in serum were measured by electrochemiluminescent assays.


RESULTS
Systemic increases of IL-6 peaked significantly at 10h compared to baseline ("ZincZinc": P=0.0005 (median increase (m. incr.)=1.36pg/mL); "ZincAlu": P=0.0012 (m. incr.=1.48pg/mL); "AluBronze": P=0.0005 (m. incr.=2.66pg/mL)). At 29h, CRP and serum amyloid A (SAA) increased distinctively ("ZincZinc": P=0.032 (m. incr.=0.65μg/mL) [CRP], 0.077 (m. incr.=0.61μg/mL) [SAA]; "ZincAlu": P=0.001 (m. incr.=1.15μg/mL) [CRP], 0.0024 (m. incr.=0.94μg/mL) [SAA]; "AluBronze": P=0.002 (m. incr.=2.5μg/mL) [CRP], 0.002 (m. incr.=0.97μg/mL) [SAA]). The median increases of CRP and IL-6 were most pronounced for the welding fume which contained besides zinc also copper (AluBronze). For differentiating AluBronze from control exposure, receiver operating characteristic (ROC) curve analysis was performed and the area under the ROC curve (AUC) for the IL-6 increases (10h versus 0h) was 0.931. The additional inflammatory mediators [vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), interferon-γ (IFN-γ), cell counts] and the lung function parameters did not show any significant changes after exposure.


CONCLUSIONS
Consistent with its role of the mediation of the acute-phase response, systemic increases of IL-6 after welding fume exposure peak at 10h before the increases of the acute-phase reactants CRP and SAA at 29h. IL-6 may represent a highly sensitive and early biomarker for the exposure to metal fumes containing zinc and copper. As IL-6, CRP and SAA are independent, strong risk markers for future cardiovascular diseases, these data may particularly be important for long-term welders with respect to their cardiovascular health.
Institute for Occupational and Social Medicine, Aachen University of Technology, Pauwelsstr. 30, D-52074, Aachen, Germany. Electronic address: RBaumann@ukaachen.de.
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R
Baumann
Institute for Occupational and Social Medicine, Aachen University of Technology, Pauwelsstr. 30, D-52074, Aachen, Germany.
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S
Joraslafsky
Institute for Occupational and Social Medicine, Aachen University of Technology, Pauwelsstr. 30, D-52074, Aachen, Germany.
A
A
Markert
Institute for Occupational and Social Medicine, Aachen University of Technology, Pauwelsstr. 30, D-52074, Aachen, Germany.
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I
Rack
Institute for Occupational and Social Medicine, Aachen University of Technology, Pauwelsstr. 30, D-52074, Aachen, Germany.
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S
Davatgarbenam
Institute for Occupational and Social Medicine, Aachen University of Technology, Pauwelsstr. 30, D-52074, Aachen, Germany.
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V
Kossack
ISF-Welding and Joining Institute, Aachen University of Technology, Pontstraße 49, D-52062 Aachen, Germany.
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B
Gerhards
Institute for Occupational and Social Medicine, Aachen University of Technology, Pauwelsstr. 30, D-52074, Aachen, Germany.
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T
Kraus
Institute for Occupational and Social Medicine, Aachen University of Technology, Pauwelsstr. 30, D-52074, Aachen, Germany.
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P
Brand
Institute for Occupational and Social Medicine, Aachen University of Technology, Pauwelsstr. 30, D-52074, Aachen, Germany.
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M
Gube
D000328:Adult; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood*; D001772:Blood Cell Count; D002097:C-Reactive Protein / Q000378:metabolism; D003300:Copper / Q000633:toxicity; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D019570:Inhalation Exposure / Q000009:adverse effects*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D018570:Risk Assessment; D013147:Spirometry; D014896:Welding; D015032:Zinc / Q000633:toxicity*
D000395:Air Pollutants, Occupational; D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D003300:Copper; D002097:C-Reactive Protein; D015032:Zinc
Acute phase response; Copper; IL-6; Inhalation exposure; Preventive risk marker; Zinc