PULMONARY RESPONSES TO PURIFIED ZINC-OXIDE FUME

Background: Metal fume fever is a flu-like illness caused by zinc oxid e fume inhalation and mediated by unknown mechanisms. It is one of a g roup of work-related febrile inhalational syndromes. We studied bronch oalveolar lavage (BAL) obtained from cigarette smoking and nonsmoking human volunteers after controlled exposure to purified zinc oxide fume to explore the possible roles of proinflammatory cytokines in this co ndition. Methods: We studied 14 volunteers after inhalation exposure t o purified zinc oxide fume and after sham exposure to air, The mean cu mulative exposure was 537+/-232 mg min per cubic meter elemental zinc, Twenty hours after exposure we performed BAL. We analyzed BAL cells a nd studied BAL supernatant for cytokines including tumor necrosis fact or-alpha (TNF alpha), interleukin(IL)-8, and IL-1 by enzyme-linked imm unosorbant assay (ELISA). Results: Polymorphonuclear leukocytes (PMNs) were significantly increased in the BAL fluid obtained post-exposure compared to sham (mean difference =41.3+/-16.8x10(3) per mL; p<0.05). Cumulative zinc exposure positively correlated with exposure-sham diff erences in BAL supernatant concentrations of both TNF (r(2)=0.58; p=.0 02) and IL-8 (r(2)=0.44, p=0.01). Exposure-sham concentration differen ces in BAL supernatant IL-8 and BAL PMNs were also positively correlat ed (r(2)=0.60; p<0.001). Cigarette smoking was not associated with exp osure-sham differences in BAL TNF or IL-8, but did demonstrate a packs -per-day dependent increase in BAL supernatant IL-1 (t=2,3, p=0.04) po st-exposure compared to sham, after taking into account the zinc expos ure response. Conclusions: Purified zinc oxide fume inhalation causes an exposure-dependent increase in proinflammatory cytokines and PMNs i n the lung, This supports a role for cytokine networking in mediating metal fume fever.