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

Respiratory exposure to zinc oxide results in metal fume fever, a flu-like illness characterized by dose-dependent increases in pulmonar 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 i vitro led to TNF release in a dose-dependent manner at 3, 8, and 2 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 = 0.529 P = 0.04). These dat 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.