TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-8 RELEASE FROM U937 HUMANMONONUCLEAR-CELLS EXPOSED TO ZINC-OXIDE IN-VITRO - MECHANISTIC IMPLICATIONS FOR METAL FUME FEVER

Respiratory exposure to zinc oxide results ist metal fume fever, a flu -like illness characterized by dose-dependent increases in pulmonary t umor necrosis factor-alpha (TNF) and interleukin-8 (IL-8). To examine whether mononuclear cells are a source of these proinflammatory cytoki nes, we exposed U937 cells to zinc oxide in vitro, Cell culture supern atant TNF and IL-8 was measured after 3, 8, and 24 hours of exposure t o zinc oxide in varying concentrations, Zinc oxide exposure in vitro l ed to TNF release in a dose-dependent manner at 3, 8 and 24 hours (ana lysis of variance [ANOVA] P = 0.0001). IL-8 demonstrated a statistical ly significant zinc exposure response cat 8 hours (ANOVA P = 0.005) an d 24 hours (ANOVA P = 0.02). IL-8 at 8 hours correlated with 3-hour TN F levels (r = 0.52, P = 0.04). These data demonstrate that in vitro zi nc oxide exposure stimulates U937 mononuclear cells to release TNF and IL-8 consistent with in vivo observations in metal fume fever.