PMID- 7552586 OWN - NLM STAT- MEDLINE DCOM- 19951121 LR - 20131121 IS - 1081-5589 (Print) IS - 1081-5589 (Linking) VI - 43 IP - 4 DP - 1995 Aug TI - Pulmonary responses to purified zinc oxide fume. PG - 371-8 AB - 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 factor-alpha (TNF alpha), interleukin(IL)-8, and IL-1 by enzyme-linked immunosorbant 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 x 10(3) per mL; p < 0.05). Cumulative zinc exposure positively correlated with exposure-sham differences in BAL supernatant concentrations of both TNF (r2 = 0.58; p = .002) and IL-8 (r2 = 0.44, p = 0.01). Exposure-sham concentration differences in BAL supernatant IL-8 and BAL PMNs were also positively correlated (r2 = 0.60; p < 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 networking in mediating metal fume fever. FAU - Kuschner, W G AU - Kuschner WG AD - Department of Medicine, University of California, San Francisco 94143-0924, USA. FAU - D'Alessandro, A AU - D'Alessandro A FAU - Wintermeyer, S F AU - Wintermeyer SF FAU - Wong, H AU - Wong H FAU - Boushey, H A AU - Boushey HA FAU - Blanc, P D AU - Blanc PD LA - eng PT - Clinical Trial PT - Controlled Clinical Trial PT - Journal Article PL - England TA - J Investig Med JT - Journal of investigative medicine : the official publication of the American Federation for Clinical Research JID - 9501229 RN - 0 (Air Pollutants, Occupational) RN - 0 (Cytokines) RN - SOI2LOH54Z (Zinc Oxide) SB - IM MH - Adult MH - Air Pollutants, Occupational/*adverse effects MH - Bronchoalveolar Lavage Fluid/chemistry MH - Cytokines/analysis/immunology MH - Dose-Response Relationship, Drug MH - Female MH - Fever/*chemically induced/immunology MH - Humans MH - Lung Diseases/*chemically induced/immunology MH - Male MH - Neutrophils/immunology MH - Occupational Diseases/*chemically induced/immunology MH - Single-Blind Method MH - Smoking MH - Syndrome MH - Zinc Oxide/*adverse effects EDAT- 1995/08/01 00:00 MHDA- 1995/08/01 00:01 CRDT- 1995/08/01 00:00 PHST- 1995/08/01 00:00 [pubmed] PHST- 1995/08/01 00:01 [medline] PHST- 1995/08/01 00:00 [entrez] PST - ppublish SO - J Investig Med. 1995 Aug;43(4):371-8.