EARLY PULMONARY CYTOKINE RESPONSES TO ZINC-OXIDE FUME INHALATION

Zinc oxide inhalation causes metal fume fever, a flu-like syndrome com mon among welders. Proinflammatory pulmonary cytokines play a role in mediating this occupational illness. The goal of this investigation wa s to characterize early pulmonary cytokine responses after experimenta l human exposure to inhaled purified zinc oxide fume. We quantified br onchoalveolar lavage (BAL) cytokine concentrations in 15 healthy volun teers 3 hr after inhalation of zinc oxide fume, We compared postexposu re cytokine responses with postsham exposure responses in the same 15 subjects. We also com pared cytokine responses with those of 14 ''late follow-up'' subjects previously studied by BAL 20 hr after zinc oxide fume exposure. Zinc oxide exposure was a statistically significant, d ose-dependent predictor of increases in BAL TNF (mean exposure-sham di fference +/- SE = 9.5 +/- 3.6 pg/mL, P = 0.02), IL-6 (mean exposure-sh am difference +/- SE = 5.5 +/- 1.8 pg/mL, P = 0.009), and IL-8 (mean e xposure-sham difference +/- SE = 64.1 +/- 23.9 pg/mL, P = 0.02). The T NF response was significantly greater at 3 hr follow-up compared with 20 hr follow-up, after adjusting for smoking status, zinc dose, and BA L macrophages (PO = 0.004). Our findings provide evidence for a pulmon ary inflammatory response 3 hr after inhalation of zinc oxide fume cha racterized by dose-dependent increases in BAL proinflammatory cytokine concentrations. These data indicate that TNF plays an important initi al role in mediating metal fume fever. (C) 1997 Academic Press.