The flu-like syndrome of fever, myalgia, and respiratory complaints called """"""""metal fume fever"""""""" is associated with inhalation of zinc oxide fume. Despite familiarity with this common condition among those exposed and among occupational health care providers, little is known about the mechanisms of its causation, the zinc oxide fume dose response relationship, and the prevention and treatment of the disorder. I hypothesize that zinc oxide fume causes the release of cytokines in the lung and that these cytokines act as endogenous pyrogens and chemotactic factors for an inflammatory response. I propose to test this hypothesis and to generate detailed dose response data for the effects observed by studying subjects performing electric arc welding on galvanized mild steel in an environmental exposure chamber. I will measure pulmonary function, including bronchial responsiveness to methacholine, at baseline, 1 hour and 20 hours after exposure. I will.carry out bronchoalveolar lavage (BAL) at 22 hours and once again between 2 to 4 months after exposure. I will analyze BAL for total cell count and differential and measure interleukin 1 (IL-1) and tumor necrosis factor (TNF) by ELISA. I will also measure mRNA for IL-1 in the BAL cells. I will correlate these physiologic and cellular effects with exposure data for zinc oxide collected by personal breathing zone monitoring and with blood zinc levels. Zinc mediated metal fume fever is one of a group of occupational disorders, including syndromes due to polymer and organic dust inhalation, suggesting common pathophysiologic mechanisms. This study addresses a pulmonary and systemic syndrome that is an important clinical problem in occupational medicine. Identifying an association with cytokines while delineating the dose response to zinc oxide fume will contribute to an understanding of the causes and prevention of metal fume fever and other similar occupational syndromes.
