Pulmonary responses to purified zinc oxide fume
Kuschner, W.G.; D'Alessandro, A.; Wintermeyer, S.F.; Wong, H.; Boushey, H.A.; Blanc, P.D.
Journal of Investigative Medicine the Official Publication of the American Federation for Clinical Research 43(4): 371-378
1995
ISSN/ISBN: 1081-5589 PMID: 7552586 Document Number: 1160
Background: Metal fume fever is a flu-like illness caused by zinc oxide fume inhalation and mediated by unknown mechanisms. It is one of a group of work-related febrile inhalational syndromes. We studied bronchoalveolar lavage (BAL) obtained from cigarette smoking and nonsmoking human volunteers after controlled exposure to purified zinc oxide fume to explore the possible roles of proinflammatory cytokines in this condition. Methods: We studied 14 volunteers after inhalation exposure to purified zinc oxide fume and after sham exposure to air. The mean cumulative exposure was 537 +- 232 mg min per cubic meter elemental zinc. Twenty hours after exposure we performed BAL. We analyzed BAL cells and studied BAL supernatant for cytokines including tumor necrosis factoralpha (TNF-alpha), interleukin(IL)-8, and IL-1 by enzyme-linked immunosorbent assay (ELISA). Results: Polymorphonuclear leukocytes (PMNs) were significantly increased in the BAL fluid obtained post-exposure compared to sham (mean difference =41.3 +- 16.8 times 10-3 per mL; p lt 0.05). Cumulative zinc exposure positively correlated with exposure-sham differences in BAL supernatant concentrations of both TNF (r-2 =0.58; p=.002) and IL-8 (r-2 =0.44, p =0.01). Exposure-sham concentration differences in BAL supernatant IL-8 and BAL PMNs were also positively correlated (r-2=0.60; p lt 0.001). Cigarette smoking was not associated with exposure-sham differences in BAL TNF or IL-8, but did demonstrate a packs-per-day dependent increase in BAL supernatant IL-1 (t=2.3, p=0.04) post-exposure compared to sham, after taking into account the zinc exposure response. Conclusions: Purified zinc oxide fume inhalation causes an exposure-dependent increase in proinflammatory cytokines and PMNs in the lung. This supports a role for cytokine net-working in mediating metal fume fever.
Document emailed within 1 workday
