The influence of silicone implantation on murine lupus in MRL lpr/lpr mice.

ABSTRACT

OBJECTIVE: The use of silicone breast implants has been implicated in the development of autoimmune connective tissue diseases including systemic lupus erythematosus (SLE). We examined the influence of implanted silicones in MRL lpr/lpr and MRL +/+ mice, to determine whether silicone increases autoimmunity and exacerbates experimental lupus. METHODS: Mice were implanted with either silicone gel or silicone oil (polydimethylsiloxane; PDMS), while saline injected mice were used as controls. Proteinuria levels, palpation of lymphadenopathy, serum autoantibodies, circulating cytokines, and weight change were monitored for 18 weeks, when terminal glomerulonephritis was evaluated by histopathological techniques. Proteins were extracted from the surface of recovered implants, and the composition and immune reactive status of the silicone-binding proteins (SBP) were investigated. RESULTS: No adverse influence of silicone gel or silicone oil on the clinical aspects of lupus was observed. However, anti-DNA antibodies were significantly increased in MRL mice implanted with silicone gel compared to the control animals, and rheumatoid factor titers were modestly increased in implanted MRL lpr/lpr mice. Serum cytokine levels were influenced by silicone implantation in MRL lpr/lpr mice (but not MRL +/+ mice), with interleukin 1 (IL-1) levels increased in gel implanted animals and IL-2 levels elevated in PDMS (silicone oil) implanted mice. Different SBP were detected on implants recovered from MRL lpr/lpr mice compared with MRL +/+ mice, and Western blotting revealed the presence of strong autoantibodies to SBP in sera from MRL lpr/lpr mice, but not MRL +/+ mice. CONCLUSION: These findings suggest that silicone implantation may influence immunological responses during murine lupus, including the provocation or exacerbation of autoantibodies. However, these immune modifications did not appear to influence the clinical variables of this experimental lupus model.