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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

Kuschner, Ware G. MD; D'Alessandro, Alessandra MD; Hambleton, Julie MD; Blanc, Paul D. MD

Journal of Occupational and Environmental Medicine: May 1998 - Volume 40 - Issue 5 - p 454-459
Original Articles

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.

From the Division of Occupational and Environmental Medicine (Dr Kuschner, Dr D'Alessandro, Dr Blanc), the Division of Pulmonary and Critical Care Medicine (Dr Kuschner, Dr Blanc), and the Division of Hematology and Oncology(Dr Hambleton), Department of Medicine, and the Cardiovascular Research Institute (Dr Kuschner, Dr D'Alessandro, Dr Blanc), University of California San Francisco, San Francisco, Calif.

Address correspondence to: Paul D. Blanc, MD, MSPH, Box 0924, University of California, San Francisco, CA 94143-0924.

© Williams & Wilkins 1998. All Rights Reserved.