Experimental research into the pathogenesis of cobalt/hard metal lung disease

In recent years clinical, epidemiological and experimental evidence has accumulated indicating that cobalt metal particles, when inhaled in association with other agents such as metallic carbides (hard metals) or diamond dust, may produce an interstitial lung disease termed "hard metal disease" or "cobalt lung". This article summarizes the progress accomplished in our two laboratories to understand the pathogenesis of this disease. Gaps and weaknesses in our current knowledge have also been highlighted in order to suggest potential avenues for further research. Whilst animal models have proved useful for the demonstration of the toxic synergy between cobalt and carbides (e.g. tungsten carbide), most animal models have remained descriptive and have not provided information on the mechanism for this synergy. In particular, the bizarre multinucleated giant cells which are an important hallmark of the human disease, have not been reproduced consistently in experimental animals. Since cobalt is a known sensitizer, there may also be a need to develop experimental models to test the possible involvement of immunological mechanisms in the pathogenesis of the interstitial disease. In vitro systems including macrophage cell cultures and physico-chemical tests have been useful to investigate the mechanism underlying the toxic synergy. The recent finding that, in vitro, cobalt and metallic carbides interact with oxygen to produce toxic activated oxygen species opens a new avenue of research and may offer an alternative interpretation of the fact that only a limited proportion of exposed workers develop interstitial disease. Besides the possible involvement of immunological mechanisms, it may be speculated that individuals with a lower antioxidant defence are more susceptible to the toxic effect of activated oxygen species produced by cobalt-containing dusts from hard metal.

This article has been cited by other articles:

				R. Colognato, A. Bonelli, J. Ponti, M. Farina, E. Bergamaschi, E. Sabbioni, and L. Migliore Comparative genotoxicity of cobalt nanoparticles and ions on human peripheral leukocytes in vitro Mutagenesis, September 1, 2008; 23(5): 377 - 382. [Abstract] [Full Text] [PDF]

				B. Nemery and J. L. Abraham Hard Metal Lung Disease: Still Hard to Understand Am. J. Respir. Crit. Care Med., July 1, 2007; 176(1): 2 - 3. [Full Text] [PDF]

				H. Moriyama, M. Kobayashi, T. Takada, T. Shimizu, M. Terada, J.-I. Narita, M. Maruyama, K. Watanabe, E. Suzuki, and F. Gejyo Two-dimensional Analysis of Elements and Mononuclear Cells in Hard Metal Lung Disease Am. J. Respir. Crit. Care Med., July 1, 2007; 176(1): 70 - 77. [Abstract] [Full Text] [PDF]

				J. W. Choi, K. S. Lee, M. P. Chung, J. Han, M. J. Chung, and J. S. Park Giant Cell Interstitial Pneumonia: High-Resolution CT and Pathologic Findings in Four Adult Patients Am. J. Roentgenol., January 1, 2005; 184(1): 268 - 272. [Abstract] [Full Text] [PDF]

				K. Gamerdinger, C. Moulon, D. R. Karp, J. van Bergen, F. Koning, D. Wild, U. Pflugfelder, and H. U. Weltzien A New Type of Metal Recognition by Human T Cells: Contact Residues for Peptide-independent Bridging of T Cell Receptor and Major Histocompatibility Complex by Nickel J. Exp. Med., May 19, 2003; 197(10): 1345 - 1353. [Abstract] [Full Text] [PDF]

				J. Araya, M. Maruyama, A. Inoue, T. Fujita, J. Kawahara, K. Sassa, R. Hayashi, Y. Kawagishi, N. Yamashita, E. Sugiyama, et al. Inhibition of proteasome activity is involved in cobalt-induced apoptosis of human alveolar macrophages Am J Physiol Lung Cell Mol Physiol, October 1, 2002; 283(4): L849 - L858. [Abstract] [Full Text] [PDF]

				T Kraus, P Schramel, K H Schaller, P Zobelein, A Weber, and J Angerer Exposure assessment in the hard metal manufacturing industry with special regard to tungsten and its compounds Occup. Environ. Med., October 1, 2001; 58(10): 631 - 634. [Abstract] [Full Text] [PDF]

				K. B. Baumgartner, J. M. Samet, D. B. Coultas, C. A. Stidley, W. C. Hunt, T. V. Colby, J. A. Waldron, and Collaborating Centers Occupational and Environmental Risk Factors for Idiopathic Pulmonary Fibrosis: A Multicenter Case-Control Study Am. J. Epidemiol., August 15, 2000; 152(4): 307 - 315. [Abstract] [Full Text] [PDF]