Pulmonary responses to purified zinc oxide fume.
BACKGROUND
Metal fume fever is a flu-like illness caused by zinc oxide fume inhalation and mediated by unknown mechanisms. It is one of a group of work-related febrile inhalational syndromes. We studied bronchoalveolar 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 condition.


METHODS
We studied 14 volunteers after inhalation exposure to purified zinc oxide fume and after sham exposure to air. The mean cumulative exposure was 537 +/- 232 mg min per cubic meter elemental zinc. Twenty hours after exposure we performed BAL. We analyzed BAL cells and studied BAL supernatant for cytokines including tumor necrosis factor-alpha (TNF alpha), interleukin(IL)-8, and IL-1 by enzyme-linked immunosorbant assay (ELISA).


RESULTS
Polymorphonuclear leukocytes (PMNs) were significantly increased in the BAL fluid obtained post-exposure compared to sham (mean difference = 41.3 +/- 16.8 x 10(3) per mL; p < 0.05). Cumulative zinc exposure positively correlated with exposure-sham differences in BAL supernatant concentrations of both TNF (r2 = 0.58; p = .002) and IL-8 (r2 = 0.44, p = 0.01). Exposure-sham concentration differences in BAL supernatant IL-8 and BAL PMNs were also positively correlated (r2 = 0.60; p < 0.001). Cigarette smoking was not associated with exposure-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) post-exposure compared to sham, after taking into account the zinc exposure response.


CONCLUSIONS
Purified zinc oxide fume inhalation causes an exposure-dependent increase in proinflammatory cytokines and PMNs in the lung. This supports a role for cytokine networking in mediating metal fume fever.
Kuschner
W G
WG
Department of Medicine, University of California, San Francisco 94143-0924, USA.
D'Alessandro
A
A
Wintermeyer
S F
SF
Wong
H
H
Boushey
H A
HA
Blanc
P D
PD
D000328:Adult; D000395:Air Pollutants, Occupational / Q000009:adverse effects*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005334:Fever / Q000139:chemically induced* / Q000276:immunology; D006801:Humans; D008171:Lung Diseases / Q000139:chemically induced* / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D009784:Occupational Diseases / Q000139:chemically induced* / Q000276:immunology; D016037:Single-Blind Method; D012907:Smoking; D013577:Syndrome; D015034:Zinc Oxide / Q000009:adverse effects*
D000395:Air Pollutants, Occupational; D016207:Cytokines; D015034:Zinc Oxide