An Experimental Human Model of Metal Fume Fever
Objective: To examine the pathogenesis of metal fume fever in humans by studying functional, cellular, and biochemical responses after exposure to zinc welding fume.
Design: Clinical experimental study.
Participants: We studied 14 welders recruited through public advertisements.
Interventions: Participants welded galvanized steel.
Measurements: We measured lung volumes, airflow, diffusing capacity for carbon monoxide, and airway reactivity at baseline as well as either 6 or 20 hours after welding. We carried out bronchoalveolar lavage either 8 hours (early follow-up, 5 participants) or 22 hours (late follow-up, 9 participants) after welding, assaying the fluid for total and differential cell counts and bronchoalveolar lavage supernatant concentrations of interleukin-1 and tumor necrosis factor (TNF).
Main Results: Changes in pulmonary function and airway reactivity were minimal. Cumulative zinc exposure and polymorphonuclear leukocyte count in bronchoalveolar lavage fluid at late (r = 0.87; P < 0.01) and early (r = 0.93; P < 0.05) follow-up were positively correlated. Among the late follow-up group, the mean proportion of polymorphonuclear leukocytes was 37% (range, 19% to 63%), a statistically greater proportion than the 9% (range, 2% to 21%) seen among the early follow-up group (P < 0.05). We did not detect TNF or more than a trace amount of interleukin-1 in the bronchoalveolar lavage supernatant.
Conclusions: Zinc oxide welding fume was associated with a marked dose-dependent increase in the number of polymorphonuclear leukocytes recovered in bronchoalveolar lavage fluid 22 hours after exposure but was not associated with a clinically significant change in pulmonary function or airway reactivity. Although we did not identify increases in either interleukin-1 or TNF levels in bronchoalveolar lavage fluid, cytokines or a cytokine-like mechanism may mediate the syndrome of metal fume fever.
References
- 1.
. Occupational Exposure to Zinc Oxide. Cincinnati: U.S. Department of Health, Education, and Welfare; 1975. Google Scholar - 2.
Meuller E and Seger D . Metal fume fever—a review. J Emerg Med. 1985;2:271-4. CrossrefMedlineGoogle Scholar - 3.
Litovitz T, Schmitz B, and Holm K . 1988 annual report of the American Association of Poison Control Centers National Data Collection System. Am J Emerg Med. 1989;7:495-545. CrossrefMedlineGoogle Scholar - 4.
Lam H, Conner M, Rogers A, Fitzgerald S, and Amdur M . Functional and morphologic changes in the lungs of guinea pigs exposed to freshly generated ultrafine zinc oxide. Toxicol Appl Pharmacol. 1985;78:29-38. CrossrefMedlineGoogle Scholar - 5.
Conner M, Flood W, Rogers A, and Amdur M . Lung injury in guinea pigs caused by multiple exposures to ultrafine zinc oxide: changes in pulmonary lavage fluid. J Toxicol Environ Health. 1988;25:57-69. CrossrefMedlineGoogle Scholar - 6.
Volgelmeier C, Konig G, Bencze K, and Fruhman G . Pulmonary involvement in zinc fume fever. Chest. 1987;92:946-8. CrossrefMedlineGoogle Scholar - 7.
Callender G . Acute poisoning by the zinc and antimony content of limeade prepared in a galvanized iron can. Milit Surg. 1937;80:67-71. Google Scholar - 8.
Murphy J . Intoxication following ingestion of elemental zinc. JAMA. 1970;212:2119-20. CrossrefMedlineGoogle Scholar - 9.
Brocks A, Reid H, and Glazer G . Acute intravenous zinc poisoning. Br Med J. 1977;1:1390-1. CrossrefMedlineGoogle Scholar - 10.
Lehmann K . Studien uber technisch und hygienisch wichtige Gase und Dampfe. XIV. Das giess- oder zinkfieber. Arch Hyg. 1910;72:358-81. Google Scholar - 11.
Sturgis C, Drinker P, and Thomson R . Metal fume fever: I. Clinical observations on the effect of the experimental inhalation of zinc oxide. J Ind Hyg. 1927;9:88-97. Google Scholar - 12.
Schmidt-Kehl L . Wie kann zinkoxyd bei einatmung fieber erzeugen? Zentralblatt Gewerbehygiene Unfallverhutung. 1928;5:272-3. Google Scholar - 13.
Beeckmans J and Brown J . Toxicity of catalytically active zinc oxides. Arch Environ Health. 1963;7:90-4. CrossrefGoogle Scholar - 14.
Mori T, Akashi S, and Nukada A . Effects of the inhalation of catalytically active metallic oxide fumes on rabbits. Int Arch Occup Environ Health. 1975;36:29-39. CrossrefMedlineGoogle Scholar - 15.
Taylor G . Acute systemic effects of inhaled occupational agents. In: Merchant JA, ed. Occupational Respiratory Diseases. Washington, DC: U.S. Department of Health and Human Services; 1986:607-25. Google Scholar - 16.
Drinker P, Thomson R, and Finn J . Metal fume fever: II. Resistance acquired by inhalation of zinc oxide on two successive days. J Ind Hyg. 1927;9:98-105. Google Scholar - 17.
. Criteria for a Recommended Standard: Welding, Brazing and Thermal Cutting. Cincinnati, Ohio: U.S. Department of Health and Human Services; 1988. Google Scholar - 18.
. Air contaminants—permissible exposure limits. OSHA 3112. Washington, DC: U.S. Department of Labor; 1989. Google Scholar - 19.
Crapo R, Morris A, and Gardner R . Reference Spirometrie values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis. 1981;123:659-64. MedlineGoogle Scholar - 20.
Mitchell M and Renzetti A . Evaluation of a single-breath method of measuring total lung capacity. Am Rev Respir Dis. 1968;97:571-80. MedlineGoogle Scholar - 21.
Olgivie C, Forster R, and Blakemore W . A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon dioxide. J Clin Invest. 1957;36:1-17. CrossrefGoogle Scholar - 22.
Gelb A, Gold W, Wright R, Bruch H, and Nadel J . Physiologic diagnosis of subclinical emphysema. Am Rev Repir Dis. 1971;107:50-63. Google Scholar - 23.
Seltzer J, Bigby B, and Stulbarg M . O3-induced change in bronchial reactivity to methacholine and airway inflammation in humans. J Appl Physiol. 1986;60:1321-6. CrossrefMedlineGoogle Scholar - 24.
. Bronchoalveolar lavage constituents in health individuals, idiopathic pulmonary fibrosis, and selected comparison groups. Am Rev Respir Dis. 1990;141:S165-202. Google Scholar - 25.
Malo J and Cartier A . Occupational asthma due to fumes of galvanized metal. Chest. 1987;92:375-7. CrossrefMedlineGoogle Scholar - 26.
Malo J, Malo J, Cartier A, and Dolovich J . Acute lung reaction due to zinc inhalation. Eur Respir J. 1990;3:111-4. MedlineGoogle Scholar - 27.
Morimoto A, Nakamori T, Watanabe T, Ono T, and Murakami T . Pattern differences in experimental fevers induced by endotoxin, endogenous pyrogen, and prostaglandins. Am J Physiol. 1988;254:R633-40. MedlineGoogle Scholar - 28.
Dinarello C, Cannon J, and Wolff S . New concepts on the pathogenesis of fever. Rev Infect Dis. 1988;10:168-89. CrossrefMedlineGoogle Scholar - 29.
Beutler B and Cerami A . The biology of cachectin/TNF—a primary mediator of the host response. Annu Rev Immunol. 1989;7:625-55. CrossrefMedlineGoogle Scholar - 30.
Neta R and Oppenheim J . Why should internists be interested in interleukin-1? [Editorial]. Ann Intern Med. 1988;109:1-3. LinkGoogle Scholar - 31.
Moser R, Schleiffenbaum B, GroscurtH P, and Fehr J . Interleukin 1 and tumor necrosis factor stimulate human vascular endothelial cells to promote transendothelial neutrophil passage. J Clin Invest. 1989;83:444-55. CrossrefMedlineGoogle Scholar - 32.
Wankowicz Z, Megyeri P, and Issekutz A . Synergy between tumour necrosis factor alpha and interleukin-1 in the induction of polymorphonuclear leukocyte migration during inflammation. J Leukoc Biol. 1988;43:349-56. CrossrefMedlineGoogle Scholar - 33.
Morimoto A, Sakata Y, Watanabe T, and Murakami N . Characteristics of fever and acute-phase response induced in rabbits by IL-1 and TNF. Am J Physiol. 1989;256:R35-41. MedlineGoogle Scholar - 34.
Bibby D and Grimble R . Temperature and metabolic changes in rats after various doses of tumour necrosis factor alpha. J Physiol (Lond). 1989;410:367-80. CrossrefGoogle Scholar - 35.
Winchurch R, Togo J, and Adler W . Supplemental zinc (Zn2+) restores antibody formation in cultures of aged spleen cells. II. Effects on mediator production. Eur J Immunol. 1987;17:127-32. CrossrefMedlineGoogle Scholar - 36.
Scuderi P . Differential effects of copper and zinc on human peripheral blood monocyte cytokine secretion. Cell Immunol. 1990; 126:391-405. CrossrefMedlineGoogle Scholar - 37.
Tanaka Y, Shiozawa S, Morimoto I, and Fujita T . Role of zinc in interleukin 2 (IL-2)-mediated T-cell activation. Scand J Immunol. 1990;31:547-52. CrossrefMedlineGoogle Scholar - 38.
Vacheron F, Rudent A, Perin S, Labarre C, Quero A, and Guenounou M . Production of interleukin 1 and tumour necrosis factor activities in bronchoalveolar washings following infection of mice by influenza virus. J Gen Virol. 1990;71:477-9. CrossrefMedlineGoogle Scholar - 39.
Nelson S, Bagby G, Bainton B, Wilson L, Thompson J, and Summer W . Compartmentalization of intraalveolar and systemic lipopolysaccharide-induced tumor necrosis factor and the pulmonary inflammatory response. J Infect Dis. 1989;159:189-94. CrossrefMedlineGoogle Scholar - 40.
Wilmott R, Kassab J, Kilian P, Benjamin W, Douglas S, and Wood R . Increased levels of interleukin-1 in bronchoalveolar washings from children with bacterial pulmonary infections. Am Rev Respir Dis. 1990;142:365-8. CrossrefMedlineGoogle Scholar - 41.
Siler T, Swierkosz J, Hyers T, Fowler A, and Webster R . Immunoreactive interleukin-1 in bronchoalveolar lavage fluid of highrisk patients and patients with the adult respiratory distress syndrome. Exp Lung Res. 1989;15:881-94. CrossrefMedlineGoogle Scholar - 42.
Pernis B, Vigliani E, Cavagna G, and Finulli M . Endogenous pyrogen in the pathogenesis of zinc-fume fever. Clin Lavoro. 1960;51:579-86. Google Scholar - 43.
Marchat-Amuroso B, de Rochemonteix-Galve B, Dayet J, and Rylander R . Tumor necrosis factor and interleukin-1 in guinea pig lung lavage cells after inhalation of endotoxin [Abstract]. Am Rev Respir Dis. 1990;141:A423. Google Scholar - 44.
Ryan L and Karol M . Release of tumor necrosis factor from guinea pig alveolar macrophages following in vitro exposure to cotton dust [Abstract]. Am Rev Respir Dis. 1990;141:A678. MedlineGoogle Scholar - 45.
Lecours R, Laviolette M, and Cormier Y . Bronchoalveolar lavage in pulmonary mycotoxicosis (organic dust toxic syndrome). Thorax. 1986;41:924-6. CrossrefMedlineGoogle Scholar - 46.
Baggiolini M, Walz A, and Kunkel S . Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989;84:1045-9. CrossrefMedlineGoogle Scholar - 47.
Larsen C, Zachariae C, and Mukaida N . Proinflammatory cytokines interleukin 1 and tumor necrosis factor induce cytokines that are chemotactic for neutrophils, T cells, and monocytes. In: Melli M, Parente L, eds. Cytokines and Lipocortins in Inflammation and Differentiation. New York: Wiley-Liss; 1990:419-31. Google Scholar - 48.
Kunkel S, Streiter R, and Chensue S . Tumor necrosis factor-alpha, interleukin-8, and chemotactic cytokines. In: Melli M, Parente L, eds. Cytokines and Lipocortins in Inflammation and Differentiation. New York: Wiley-Liss; 1990:433-44. Google Scholar
This content is PDF only. To continue reading please click on the PDF icon.
Author, Article and Disclosure Information
From the University of California, San Francisco, San Francisco, California. For current author addresses, see end of text.

Submit a Comment
Contributors must reveal any conflict of interest. Comments are moderated.