Immunotoxicity of silicone: implications of oxidant balance towards adjuvant activity.
A variety of mechanisms can be proposed to explain the potential effects of silicone and silicone by-products on the immune response. In this paper, we discuss information on the chemistry of silicon and silicone gels/elastomers, and the manufacture of silicone breast implants as they pertain to the bioreactivity of silicone. Moreover, with reference to silicone-mediated human adjuvant disease, an overview of experimental adjuvant-induced arthritis is presented; comparisons with graft-versus-host disease and chemically induced autoimmunity then follow. Particular attention is paid to similarities in the characteristics of silicone and classic lipid adjuvants. For example, macrophage activation is presumed to be a central event in silicone-induced autoimmunity. Since those genes uniquely expressed in macrophages activated by plastic adherence are similar to those induced by lipopolysaccharide, adherence to silicone rubber may initiate an inflammatory response by the same mechanism. Macrophage effects would also include the erosion of implants through the generation of oxidants and localized pH changes. The degradation products of silicone are also implicated in the adjuvant effects of silicone implants. There is evidence to suggest that oxidants produced by inflammatory cells preferentially inactivate CD8+ suppressor T cells. This could then lead to an inflammatory state, perhaps through oxidant-induced transcription factors such as NF-kB, resulting in a long-term pro-oxidant imbalance that manifests itself as a breakdown in immunological self-tolerance. The authors hypothesize that autoreactivity following oxidant stress evolved to enhance inflammatory repair mechanisms after tissue, cell or molecular damage by oxidants.
Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California, Davis 95616.
S H
SH
Yoshida
S S
SS
Teuber
J B
JB
German
M E
ME
Gershwin
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D015551:Autoimmunity; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000633:toxicity*; D018427:Breast Implants; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D012828:Silicones / Q000009:adverse effects* / Q000138:chemical synthesis
D001672:Biocompatible Materials; D012828:Silicones