Coalition of Silicone Survivors
Immunologic stimulation of T lymphocytes by silica after use of silicone
Douglas.R. Shanklin; David.L. Smalley; M.F. Hall; M.V. Stevens; A. Hanissian
FASEB J. 9, 424 (1995 )
Baptist Memorial Health Care Systems, Memphis, Tennessee 38105
Difficulties in showing the biologic activity of silicones in vitro have contributed to the controversy over effects
of silicone mammary implants in vivo. We adapted a standard lymphocyte stimulation test to detect evidence of
cellular immunity in patients with silicone gel implants. Initially, lymphocytes were harvested from 70 implant
patients, 76 normal controls without implants or symptoms, and 18 patients with classic rheumatic disorders and
without a history of silicone implants. The harvested lymphocytes were stimulated with PWM, PHA, Con A, and
pharmaceutical grade colloidal silicon dioxide (silica). Implant patients showed increased SI compared to
controls and those with rheumatic disorders. The mean SI of implant patients was 195.0 +/- 19.3, 18-fold that of
normal controls (< 0.0001). Patients with rheumatic disease showed the same SI as controls (P = 0.3577). A follow-
up study included 220 normal controls without implants, 942 silicone gel implant patients with demonstrable
rheumatic symptoms, and 34 implant patients without symptoms at the time of the study. The average SI for the
220 normal controls was 10.0 +/- 0.41. Among the symptomatic implant women, 860 (91.3%) had SI significantly
above those of the normal controls. Of these, 171 (18.2%) had SI between 25 and 50, 316 (33.5%) had SI between
50 and 100, and 373 (39.6%) had SI over 100. The data presented confirms that silicone implant patients respond
immunologically to the silicon dioxide contained in mammary prostheses.
COSSkids is onderdeel van Coalition of Silicone Survivors - Boulder Collorado USA
Prof. M.D. Douglas R. Shanklin en Prof. David. L. Smalley
Lymphocyte response to silica among offspring of silicone breast implant
D.L. Smalley, J.J. Levine, D.R. Shanklin, M.F. Hall, M.V. Stevens
Immunobiology 196,567 (1996)
Baptist Memorial Healtcare System, University of Tennessee, Memphis, USA
The current study evaluated immune response to silicon dioxide in children born to women with silicone breast
implants. In part one of the study, the T lymphocytes of 21 of 24 such children were significantly stimulated by
silicon dioxide (silica). Part two consisted of eleven children, four born preimplantation and seven born
postimplantation. None of the preimplant offspring showed T cell responses to silica; five of the seven
postimplant children were positive for T cell memory for silica. Part three was a blinded study based on
statistically significant differences in T cell stimulation with silicon dioxide between postimplant children and
controls. These findings indicate a common immune reaction, that of T cell memory, occurs in mothers and their
children born after exposure to silicone mammary implants placed prior to pregnancy. Since not all such children
were breast fed the result favors transplacental passage of immunogens such as silicone oligomers or through
maternofetal cellular traffic.
The Immunopathology of siliconosis, History, clinical presentations, and relation to silicosis and the chemistry of silicon and silicone.
Douglas.R. Shanklin; David.L. Smalley
Immunol. Res, 18, 125 (1998)
Department of Pathology, University of Tennessee, Memphis, 38163, USA.
Recent evidence confirms the fundamental involvement of the human immune system in the reaction to implantation of silicone-based medical devices. An as yet-to-be particularized epitope of many complex substances sharing siloxane structures is presented through the MHC-II apparatus with development and retention of T cell memory. This memory can be tested for in practical terms using one or more forms of silica, which links the immuno-histopathology and autoimmune attributes of "silicosis" with those of "siliconosis." The lesions of siliconosis are typical of those for persistent antigens and delayed, cell mediated hypersensitivity. The basic descriptive pathology of the reaction to silicone has been known since soon after introduction of silicones in medical procedures, with the exception of some details related to the more recent discoveries on the role of cytokines in the immunopathic process. The clinical consequences of siliconosis are common and can be severe in some individuals implanted with silicone devices.
Monocyte-dependent stimulation of human T cells by silicon dioxide.
Douglas.R. Shanklin; David.L. Smalley; M.F. Hall
Pathobiology 66, 302 (1998)
Baptist Regional Laboratories, The University of Tennessee, Memphis, Tenn, USA.
Mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation from randomlyselected silicone breast implant recipients for testing. Restricted antibody to HLA-DR (28-33 kD) depleted the concanavalin A mitogenic response which was expected but failed to inhibit the proliferative response to silicon dioxide. Further testing with monoclonal antibodies to HLA-DP, -DQ, and a second - DR with specificity for the NS1 region of the MHC class II genome, all markedly inhibited proliferation of T cells despite otherwise adequate stimulation by concanavalin A or silicon dioxide. Monoclonal antibodies directed against B7-1 also inhibited proliferation of T cells following stimulation with concanavalin A or silicon dioxide. These results confirm the T-cell response to silicon dioxide is monocyte-dependent and not a superantigen as has been speculated.
Dynamics of wound healing after silicone device implantation
D.R. Shanklin; D.L. Smalley Exp. Mol.Pathol.67,26 (1999)
Department of Pathology, University of Tennessee, Memphis 38163, USA.
A large surgical wound is required for implantation of silicone mammary devices. Formation of capsules around silicone devices follows wound healing processes except that the healing is conformed and significantly delayed by the physical presence of the implant. Multilayered capsules are thicker and lymphocytic and plasmalymphocytic vasculitis, markers for delayed hypersensitivity, also correlate with thicker capsules. Polyurethane-coated devices induce very thick capsules that remain so for over 20 years. By contrast, gel and saline content devices show maximum thickness at 6. 5 years. Active T(H) lymphocyte memory does not differ by implant type for individuals with devices in place and that for gel content devices peaks at 10.5 years. There was a significant decrease in T cell indexes only after the removal of saline content devices. Comparison of the rate of formation of the periprosthetic capsule with the healing time of large wounds of similar size indicates that silicone devices interfere with the healing process, requiring substantially more time. This extended period has the potential for enhancing autoimmune conversion as a consequence of persistent delayed hypersensitivity.
Environmental immunogens and T-cell mediated responses in fibromyalgia evidence for immune dysregulation and determinants of granuloma formation.
D.Radford. Shanklin; M.V. Stevens; D.L. Smalley
Exp. Mol, Pathol. 69, 102 (2000)
Department of Pathology, University of Tennessee, Memphis, Tennessee 38163, USA.
Thirty-nine patients with fibromyalgia syndrome (FMS) according to American College of Rheumatology criteria were studied for cell-mediated sensitivity to environmental chemicals. Lymphocytes were tested by standard [(3)H]thymidine incorporation in vitro for T cell memory to 11 chemical substances. Concanavalin A (Con A) was used to demonstrate T cell proliferation. Controls were 25 contemporaneous healthy adults and 252 other concurrent standard controls without any aspect of FMS. Significantly higher (P < 0.01) stimulation indexes (SI) were found in FMS for aluminum, lead, and platinum; borderline higher (0.05 > P > 0.02) SI were found for cadmium and silicon. FMS patients showed sporadic responses to the specific substances tested, with no high-frequency result (>50%) and no obvious pattern. Mitogenic responses to Con A indicated some suppression of T cell functionality in FMS. Possible links between mitogenicity and immunogenic T cell proliferation, certain electrochemical specifics of granuloma formation, maintenance of connective tissue, and the fundamental nature of FMS are considered.
Pathogenetic and diagnostic aspects of siliconosis.
D.Radford. Shanklin; D.L. Smalley
Rev Environ Health 17, 85 (2002)
Department of Pathology, University of Tennessee, Memphis, 38163, USA.
Silicones have an adverse effect on human health well beyond that suggested by the recent superficial public controversy. The evidence for immune responses to injected/implanted silicones is extensive, detailed, often very specific, and not at all new. Comprehending the immunopathogenicity, realized and potential, of silicone has grown as our general understanding of the immune system has developed. Several major issues in furthering this comprehension pertain to the nature of the essential epitope, special risk of silicones to women, and definition of the chronic disease complex so evident clinically, one defying classification within currently traditional disease categories and states. The commentary presented here emphasizes the immunopathic evidence, explores the question of the essential epitope, estimates the minimal threshold of silicone load for immune reactivity, presents a profile of autoantibodies for siliconosis, and calls attention to specific silicone-based female contraceptive modalities. The silicone content of personal care products, not always revealed by retail package labeling, is explored as a potential sensitizing factor in the environment.
Kinetics of T lymphocyte responses to persistent antigens.
Douglas.R. Shanklin; David.L. Smalley
Exp. Mol. Pathol. 80,26 (2006)
Department of Pathology and Laboratory Medicine, University of Tennessee, Suite 599, 930 Madison Avenue, Memphis, TN
38163, USA. dshanklin@utmem,edu
Long term sequential study of immune responses in the same individuals is difficult from the time commitment required and the problem of maintaining enough subjects to provide for comparative analysis. We closely studied one hundred women with silicone mammary devices through cross sectional analysis up to 26 years post implantation and a similar sample of women to 6 years post explantation. The T cell index, calculated from tritiated thymidine incorporation during lymphoblast transformation, rose to a post implant peak at 10.5-12.0 years, falling progressively over the next 14.0-15.5 years to values indicative of probable immune quiescence. Post explantation, the index rose over the first 3 years and then sharply declined to within the range for unexposed controls. The shape of these time curves contains considerable information referent cell dynamics for both stimulatory and inhibitory factors and for demonstrating net group effects, appropriate to analysis in the cross sectional perspective. When a subset of four women was studied frequently and sequentially up to 8 years, an internal oscillatory pattern emerged, focusing attention on both the stimulatory and the inhibitory aspects of long term clonal expansion. IL-2 has stimulatory and inhibitory properties at different levels of production and is considered a prime candidate as the essential cytokine. The equations have details, however, which require exploration beyond any such provisional conclusion. The analytic process was aided by normalization of oscillatory data to eliminate subject variability and by Pareto optimization to assess the trend shown by normalization. Pareto analysis revealed two minimally coordinated oscillations, one over time and the other along net clonal expansion or decline of the siloxane specific T lymphocyte clone. The segments of the time related oscillation greatly exceeded the reaction times of cytokines currently known to be active in T cell regulation. Although the ultimate controlling factor(s) may be cytokine or chemokine combinations, the data are compatible with some more basic regulatory factor(s) of cell integrity, including limits on the number of cell divisions which can be sustained in long term immunopathic lesions, among other processes.