Date: Fri, 16 Jun 2000 14:07:09 +1200

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From: USSW

Date: Sunday, 26 July 1998 14:57

Subject: NOTES ON THE PROCEEDINGS - PART 2

NATIONAL ACADEMY OF SCIENCES

INSTITUTE OF MEDICINE

COMMITTEE ON THE SAFETY OF SILICONE BREAST IMPLANTS

SCIENTIFIC WORKSHOP - JULY 22, 1988

NOTES ON THE PROCEEDINGS - PART 2

DONALD J. SCHAEZLER, PH.D., P.E., CIH

IMMUNOLOGY

John Naim started this session with a presentation on adjuvancy effects of silicone. Adjuvancy is the NON-SPECIFIC enhancement of a SPECIFIC immune system response to an antigen. The specific response might be production of antibodies (humoral immune response), activation of T-cells (cellular immune response), an inflammatory response with the production of cytokines (immune system messenger cells). Silicone gel has been shown to be a strong humoral adjuvant and a weak cellular adjuvant; oil is a weak adjuvant; elastomer (shell) silicone has not been studied enough to say.

Key to silicones role is the formation of an emulsion with the antigen. This is usually done by homogenization of the specific antigen, e.g., bovine serum, with the silicone. This draws the criticisms that it is the oil/water emulsion that is important, not the silicone chemicals, that homogenization is not an in vivo (in the body) process, and that homogenization may alter the silicone chemicals.

A very important question is whether silicone can induce or enhance Autoimmune reactions (immune responses to "self", i.e., normal body chemicals like nucleic acids or proteins). To date, silicone has been shown in animals to have an adjuvant effect but not an induction role on its own. However, in new studies, with a different mouse as the test organism, there is possible direct induction of IgM anti-nuclear antibodies (ANA); this study is being expanded.

A new area of research is Monocyte Macrophage Activation with the Production of Cytokines. Naim's work indicates that the reaction of a protein with a hydrophobic surface (like silicone) leads to more cytosine production than without the surface. The protein is the cause of cytosine production; the silicone is an adjuvant. Other polymers, like polystyrene, have a similar, but perhaps lesser effect than silicone.

[Note: other presentations later in the day connected cytokines to possible autoimmune responses.]

SUMMARY: Naim's work indicates that silicone can act as an adjuvant in several ways and that it may be able to induce an autoimmune response directly, not just have an adjuvant effect. The mechanism may involve adsorption of proteins from the body onto the silicone surface. 

Michael Potter of NCI spoke about silicone and the induction of Plasmacytomas (types of cancers) in susceptible mice. The importance is that this is an animal model for some types of cancers in people.

The model presented is that granulomas are formed around foreign materials; the granulomas are invaded by mutant B-cells, which proliferate uncontrollably, becoming a tumor. The inflammatory response to the foreign body, including Cytokine production is important in this process. Incidentally, anti-inflammatory agents may be able to block the cancer process in the mice.

COMMENT: Potter shows another aspect of the possible role of silicone in starting an inflammatory process which leads to an immune system berration. 

Fred Miller of FDA spoke about environmental agents which can create rheumatic autoimmune (AI) deficiency conditions. Certain drugs, vinyl chloride, silica (crystalline), and infectious agents have been shown to cause these AI diseases. The issue now is: can silicone also do this?

He also began with the foreign body/inflammatory response, including the roles of phagocytes, T-cells, B-cell aggregates, and collagen proteins. The production of Monoclonal vs. Polyclonal cellular aggregates was a key distinction. And the question of whether the response can expand into a systemic response is really important.

Then he talked about dermatomyocytis symptoms in response to Breast Implants and the correlation of symptoms to individual genetic markers of immune system type (Human Leukocyte Antigens, HLA).

COMMENT: This all seemed very important, but the presentation was too rapid and too advanced to capture the import entirely.