title: Tumor necrosis factor-alpha and interleukin-8 release from U937 human mononuclear cells exposed to zinc oxide in vitro. Mechanistic implications for metal fume fever.
abstract: Respiratory exposure to zinc oxide results in metal fume fever, a flu-like illness characterized by dose-dependent increases in pulmonary tumor necrosis factor-alpha (TNF) and interleukin-8 (IL-8). To examine whether mononuclear cells are a source of these proinflammatory cytokines, we exposed U937 cells to zinc oxide in vitro. Cell culture supernatant TNF and IL-8 was measured after 3, 8, and 24 hours of exposure to zinc oxide in varying concentrations. Zinc oxide exposure in vitro led to TNF release in a dose-dependent manner at 3, 8, and 24 hours (analysis of variance [ANOVA] P = 0.0001). IL-8 demonstrated a statistically significant zinc exposure response at 8 hours (ANOVA P = 0.005) and 24 hours (ANOVA P = 0.02). IL-8 at 8 hours correlated with 3-hour TNF levels (r = 0.52, P = 0.04). These data demonstrate that in vitro zinc oxide exposure stimulates U937 mononuclear cells to release TNF and IL-8 consistent with in vivo observations in metal fume fever.
authors.affiliation: Division of Occupational and Environmental Medicine, University of California San Francisco 94143-0924, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Kuschner
authors.forename: A
authors.initials: A
authors.lastname: D'Alessandro
authors.forename: J
authors.initials: J
authors.lastname: Hambleton
authors.forename: P D
authors.initials: PD
authors.lastname: Blanc
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008670:Metals / Q000506:poisoning; D009784:Occupational Diseases / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015034:Zinc Oxide / Q000009:adverse effects*
chemical_list: D016209:Interleukin-8; D008670:Metals; D014409:Tumor Necrosis Factor-alpha; D015034:Zinc Oxide