The influence of silicone implantation on type II collagen‐induced arthritis in mice

Abstract

Objective. To determine whether silicone implantation exacerbates autoimmune disease in a murine experimental model of arthritis.Methods. DBA/l mice were implanted with silicone in the form of an elastomer, gel, or oil, and immunized with type I1 collagen. The influence of silicone implantation on collagen-induced arthritis and the immune response to type I1 collagen were determined by comparison against control mice receiving sham implantation. Adjuvant effects of silicone implantation were examined by measuring cytokine levels in implanted animals and assessing autoantibodies against proteins extracted from recovered silicone implants.Results. No adverse influence of silicone implantation on the clinical aspects of collagen-induced arthritis was observed. Further, polydimethylsiloxane silicone oil failed to serve as an adjuvant in the immune or arthritogenic response to type I1 collagen in mice. Cytokine analysis indicated that tumor necrosis factor a levels were lower and interleukin-2 levels were higher in silicone-implanted mice. The development of arthritis increased protein binding to implanted elastomers and gel, and autoantibodies against silicone-bound proteins were present in sera from arthritic mice and absent in sera from nonarthritic mice.Conclusion. The data suggest that silicone implantation may result in autoantibodies against silicone-bound proteins, and the presence of arthritis may either provoke or increase the level of such autoantibodies. However, silicone implantation did not inMs. Schaefer is the recipient of a Graduate Research Assistantship provided by Hutzel Hospital.

Influence of long term silicone implantation on type II collagen induced arthritis in mice

“…Serum concentrations of interleukin 1β (IL1β), tumour necrosis factor α (TNFα), IL2, and gamma interferon (IFNγ) were determined using commercial ELISA assays (Genzyme, Cambridge, MA) as described previously 13. Serum concentrations of IL4, IL5, IL10 were determined using a similar capture ELISA technique, using specific antibody pairs (Pharmingen, San Diego, CA).…”

“…Recovered implants were pooled into groups: (1) silicone elastomer implants from mice with arthritis, (2) silicone elastomer implants from mice without arthritis, (3) gel implants from mice with arthritis, (4) gel implants from mice without arthritis, (5) oil implants recovered from mice with arthritis and (6) oil implants recovered from mice without arthritis. Proteins were recovered from implants using techniques described previously,13 which are based upon exposure to glycine-HCl buffer (pH2.8) followed by immersion in 4M guanidine solution. Recovered protein extract solutions were concentrated, and the amount of protein extracted from the silicone implants was determined by a BCA protein assay commercial kit.…”

“…In addition to the response to collagen, DBA/1 mice develop arthritis on injection with the mineral oil pristane,11 and also develop arthritis spontaneously at a low frequency,12which suggests that this strain expresses an underlying susceptibility to joint disease. Short-term silicone implantation in DBA/1 mice did not result in an increase in the incidence or severity of arthritis 13. However, silicone implantation did change cytokine levels and resulted in the development of novel autoantibodies directed against silicone bound proteins (SBPs).…”

Dietary Silica Modifies the Characteristics of Endothelial Dilation in Rat Aorta

“…One possible explaination of this omission might be its frequent use in clinics for therapeutic and cosmetic purposes. The other reason is the lack of a direct link between symptoms and blood Si, because the normal blood Si levels are found in those subjected to occupationally, medically, or dietary high Si (Teuber et al 1995;Peters et al 1999;Schaefer et al 1999;Lugowski et al 2000). Normal blood Si levels mask any connection between Si and the observed symptoms.…”

“…Besides environmental or oral exposure (Calvert et al 1997;Gregorini et al 1997;Fubini and Hubbard 2003), the human body, especially women's, are subjected to long-term Si through large or small joint prothesis, silicon-gel filled breast implants, or Si injections (Teuber et al 1995;Peters et al 1999;Schaefer et al 1999;Lugowski et al 2000).…”