Immune response to zinc oxide inhalation in metal fume fever, and the possible role of IL-17f

Abstract

Metal fume fever (MFF) is a work-related disease caused by the inhalation of metal particles, including zinc oxide. Chronic asthma may develop as a long-term consequence of exposure, particularly for welders and metal workers who are most at risk. In this study, we investigated the effects of ZnO fume inhalation on multiple inflammation-related cytokine- and cytokine receptor genes in mice from lung and lymph node samples, to explore the role of these in the pathogenesis of MFF. In our experiments, the animals were treated with a sub-toxic amount of ZnO fume for 4 h a day for 3 consecutive days. Sampling occurred 3 and 12 h post-treatment. We are the first to demonstrate that ZnO inhalation causes extremely increased levels of IL-17f gene expression at both sampling time points, in addition to increased gene expression rates of several other interleukins and cytokines, such as IL-4, IL-13, CXCL5, CSF-3, and IFN-γ. Our animal experiment provides new insights into the immunological processes of early metal fume fever development. IL-17f plays a crucial role in connecting immunological and oxidative stress events. The increased levels of IL-4 and IL-13 cytokines may explain the development of long-term allergic asthma after exposure to ZnO nanoparticles, which is well-known among welders, smelters, and metal workers.