Abstract
An asymptomatic systemic inflammation after exposure to zinc- and copper-containing welding fumes has been described as mild form of metal fume fever in recent studies. Since chronic systemic inflammation leads to a higher cardiovascular risk, examining the inflammation with the underlying pathomechanism is necessary to estimate and hopefully prevent long-term effects of welding. We established a whole blood assay to investigate the effects of zinc- and copper-containing welding fume particles on the blood immune response. Increased levels of IL-6, IL-8, TNFα and IL-1β determined after 24 hours of exposure indicated an acute systemic inflammatory reaction. In vitro increases of IL-6 were comparable to in vivo increases of serum IL-6 levels in a study with welding fume exposure of human subjects. Inhibition of PTP1B was identified as one pathway responsible for the effects of zinc- and copper-containing welding fumes and therefore welding fume fever. In conclusion, the whole blood assay is a reliable and feasible method to investigate effects of zinc- and copper-containing welding fumes on the immune system and as a surrogate for systemic inflammation and welding fume fever. Future research can utilize whole blood assays to reduce and partially replace human exposure studies for further investigations of welding fume fever.
Highlights
Metal fume fever is a complex of symptoms including fever, headache, myalgia, fatigue and dyspnoea, typically occurring after exposure to welding fumes[1]
The present study introduces the whole blood assay as feasible method to investigate the effects exerted by zincand copper-containing welding fumes on the blood immune system
The incubation of welding fume particles with whole blood resulted in a considerable increase of cytokines and chemokines IL-6, IL-8, TNF-α, IL-1β, IL-13 and IL-10
Summary
Metal fume fever is a complex of symptoms including fever, headache, myalgia, fatigue and dyspnoea, typically occurring after exposure to welding fumes[1]. In studies with healthy human volunteers, a subclinical systemic inflammation indicated by an increase of C-reactive protein (CRP) serum levels could be observed 24 hours after exposure to welding fumes from a metal inert gas brazing (MIG) process containing zinc and copper[6,7]. To elucidate the origin of the inflammatory response resulting in the typical symptoms shown by welders after exposure to zinc- and copper-containing welding fumes the respiratory tract including the lungs as the main uptake route of the welding fumes were investigated in prior studies. The effects of zinc- and copper-containing welding fumes have been investigated in precision-cut lung slices (PCLS)[14]. The effects of welding fumes on the lungs cannot consistently explain the observed induced systemic inflammation resulting in symptoms typical for metal fume fever. The mechanism by which zinc- and copper-containing welding fumes induce the inflammation was investigated
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