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CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, Mar. 1996, p. 156–161 Vol. 3, No. 21071-412X/96/$04.0010Copyright q 1996, American Society for MicrobiologyPhenotype of Lymphocytes Associated with the InflammatoryReaction to Silicone Gel Breast ImplantsWILLIAM E. KATZIN,1,2* LU-JEAN FENG,2,3 MARY ABBUHL,1 AND MARY ANN KLEIN1Department of Pathology1 and Division of Plastic Surgery,3 Mt. Sinai Medical Center, and Case Western ReserveUniversity School of Medicine,2 Cleveland, OhioReceived 18 July 1995/Returned for modification 13 September 1995/Accepted 27 November 1995The tissue response to silicone gel breast implants typically includes an inflammatory infiltrate that consistsof macrophages, foreign body-type giant cells, and a variable number of lymphocytes and plasma cells. Thephenotype of the lymphocytic component was investigated with three-color flow cytometry. Lymphocytes wereobtained by collecting fluid from the space between the implant and the fibrous capsule or by washing cellsfrom the fibrous capsule at the time of implant removal with total capsulectomy. Eighty-nine percent of theimplant-associated lymphocytes were T cells. Twenty-five percent of the CD31 T cells coexpressed HLA-DRcompared with only 7.9% of matched peripheral blood lymphocytes. Sixty-eight percent of the implantassociatedT cells coexpressed CD4 and CD29, while only 3% of the T cells coexpressed CD4 and CD45RO. Theexpression of HLA-DR and the predominance of CD291 CD41 T cells indicate that there is immune activationwith the potential for stimulating antigen-specific antibody production. The role of silicone gel breast implantsin immune activation and its clinical significance require further investigation.Silicone gel-containing breast implants, introduced over 30years ago (7), have been widely used for augmentation andreconstructive mammoplasty. Recently there has been increasingconcern regarding the safety of breast implants. Most notably,a variety of rheumatic diseases, including chronic arthropathy(2, 9, 39, 46), scleroderma or systemic sclerosis (6,20, 21, 33, 36, 37, 40, 42), rheumatoid arthritis (9, 20, 40),systemic lupus erythematosus (36, 40), and Sjogren’s syndrome(20, 40) have been reported in patients with silicone gel breastimplants. However, the relationship between implants andthese connective tissue diseases is still unclear (41). Threeseparate epidemiologic studies (11, 34, 47) have not found anincreased incidence of specific rheumatic diseases in large populationsof women with silicone gel implants. The possiblerelationship between silicone breast implants and systemic diseasehas been recently reviewed by -Guerrero et al.(35).The tissue response to silicone gel-containing breast implantsincludes formation of a fibrous capsule. On the basis ofstudies with an animal model, it is likely that the capsule formsin a relatively short time—probably within 2 months (27). Thehistologic features of the fibrous capsule in women with implantshave been described previously (3, 12, 14, 15, 30, 32, 38).In addition to a band of dense fibrous tissue, the capsuleincludes a variable number of inflammatory cells. Macrophageswith abundant vacuolated cytoplasm are a relativelyconstant feature. There are often cyst-like spaces that containrefractile, nonbirefringent clear material that almost certainlyrepresents some form of silicone (1, 14, 32, 38). The inflammatoryinfiltrate also includes a variable number of lymphocytesand plasma cells (12, 16, 38).Aside from the morphologic features of the fibrous capsulethat surrounds silicone gel breast implants, very little is knownabout the nature of the inflammatory response. In an attemptto provide more specific information in this regard, we havedefined the phenotype of the lymphocytic component of thecapsular infiltrate by three-color flow cytometry.MATERIALS AND METHODSDuring the study period (1 May 1992 to 1 April 1993), a total of 209 patientsunderwent implant removal. The vast majority of these patients presented withlocal breast pain and systemic symptoms that they suspected were associated withtheir implants. Surgery in all cases was performed by one of the authors (L.-J.F.),who submitted all of the samples. All of the patients were examined by arheumatologist, internist, or neurologist prior to implant removal. Eight of the209 patients had documented autoimmune diseases which had developed afterimplantation. Three had rheumatoid arthritis, two had multiple sclerosis, onehad systemic lupus erythematosus, one had systemic lupus erythematosus andpolymyositis, and one had scleroderma. Only one of the 209 patients had evidenceof frank infection.In preliminary studies, we found that a sufficient number of lymphocytes forflow cytometric analysis could be obtained only from patients with either polyurethane-coated silicone gel breast implants or textured-surface silicone gelbreast implants. In those patients, exudative fluid was present in the spacebetween the implant and the surrounding fibrous capsule. Little or no exudativefluid or very few mechanically dislodged cells could be obtained from patientswith smooth-shell silicone gel implants. Implant-associated lymphocytes wereobtained at the time of surgical implant removal in all cases in which exudativefluid was available. In some cases, fluid was collected from the space between theimplant and the surrounding fibrous capsule and sent directly for phenotyping. Inthe other cases, the fibrous capsule was vigorously washed in RPMI 1640 mediumand the mechanically dislodged cells were immediately sent for phenotyping. Ina few cases, peri-implant fluid was sent from one breast, and a capsular wash wassent from the opposite breast of the same patient. Implant-associated cells werewashed twice in RPMI 1640 medium, and the cell pellet was resuspended in 1 mlof RPMI 1640 medium. The cell yield and viability were determined at this time.The resuspended cells were then mixed with RPMI 1640 medium containing10% fetal calf serum (Hyclone, Logan, Utah) and rocked in a 378C incubator for30 min. Cell suspensions were filtered through a 40-mm-pore-size nylon mesh(Tetco, Briar Cliffe Manor, N.Y.) and centrifuged for 5 min at 400 3 g. Cellswere then washed once in RPMI 1640 medium and resuspended in RPMI 1640medium to obtain a cell concentration of 2 3 106 cells per ml. The cells insamples with a low yield were resuspended in 1 ml of RPMI 1640 medium.In addition to the implant-associated cells, heparin-anticoagulated peripheralblood was submitted for phenotyping. Peripheral blood mononuclear cells wereisolated from heparinized blood by density gradient centrifugation (Histopaque-1077; Sigma, St. Louis, Mo.). The peripheral blood mononuclear cells wererecovered and washed twice with Hanks balanced salt solution without Ca or Mg(Gibco, Grand Island, N.Y.) at room temperature. The cell pellet was thenresuspended in 1 ml of Hanks balanced salt solution, and the cell count wasadjusted to 2 3 106 cells per ml for staining. In some cases, the lymphocytes wereseparated from whole blood by Ficoll-Hypaque density gradient centrifugationand stored in freezing medium (25% calf serum, 8% dimethyl sulfoxide, 67%* Corresponding author. Mailing address: Department of Pathology,Mt. Sinai Medical Center, One Mt. Sinai Dr., Cleveland, OH 44106.Phone: (216) 421-4403. Fax: (216) 421-3964.156Downloaded from cvi.asm.org by on January 22, 2008Dulbecco’s modified Eagle’s medium) in liquid nitrogen prior to flow cytometry.Previously frozen peripheral blood mononuclear cells were snap thawed in a378C water bath and washed twice with Dulbecco’s phosphate-buffered saline(D-PBS) without Ca or Mg (Gibco). The cell pellet was resuspended in 1 ml ofD-PBS. Viability was checked with trypan blue (Sigma).Three-color staining was performed with 20 ml of mouse monoclonal antibodies(Table 1), at an optimum titer, directly conjugated with fluorescein isothiocynate(FITC), phycoerythrin (PE [or RD1]), or peridinin chlorophyll protein(PERCP). One hundred microliters of the cell suspension was added to theappropriate tubes and mixed. The samples were then incubated at room temperatureout of direct light for 15 min with gentle vortexing at 5-min intervals.Samples with gross erythrocyte contamination or whole-blood samples werelysed by incubation with FACSLyse (Becton Dickinson, San , Calif.). Cellswere then washed twice with Hanks balanced salt solution with 1% bovine serumalbumin (BSA) (Sigma) and 0.1% sodium azide (Fisher, Pittsburgh, Pa.). Thecell pellet was then resuspended in 0.5 ml of D-PBS with 1% BSA and 1%ultrapure electron microscopy-grade formaldehyde (Methanol Free; Polysciences,Washington, Pa.) for fixation. Negative controls, consisting of isotypicallymatched nonimmune mouse immunoglobulin, were used to position thecursors that defined positive and negative cells. Positive controls consisted ofperipheral blood lymphocytes from healthy donors. Cells were analyzed on aFACScan flow cytometer with an argon ion laser emitting at 498 nm (BectonDickinson). Gates for acquisition of data were set by light scatter characteristicsand were verified by back-gating with cells stained for CD45 and CD14. A totalof 10,000 gated events were acquired with LYSYS analysis software (BectonDickinson), yielding a percentage of total cells positive for each antigen. In thefew samples that contained too few cells to acquire 10,000 events, as many gatedcells as possible were acquired. Analysis of data was performed with PAINT-AGATEsoftware (Becton Dickinson).Statistical comparisons between the phenotypes of the implant-associated lymphocytesand those of the peripheral blood were analyzed with the paired t test.Statistical comparisons between the phenotypes of the peripheral blood lymphocytesof the patients and those of the healthy controls were analyzed with theunpaired t test.RESULTSAll cases accessioned between 1 May 1992 and 1 April 1993for which cells were submitted for phenotypic analysis by flowcytometry were included in this study, with the following exceptions.In three cases, there was an insufficient number ofcells to provide complete and reliable phenotypic data. In fouradditional cases, the percentage of events in the lymphocytegate that were CD451 and CD142 was less than 80%. In allcases included in the study, that percentage was greater than85%. In three cases, separate samples were submitted from theright and left breasts. In those cases, there were no significantphenotypic differences between the two samples, and only thedata from the sample submitted first were considered for statisticalcalculations regarding the paired peripheral blood samples.There were no phenotypic differences between exudativefluid samples and capsular wash samples. In one case, theperipheral blood lymphocytes that had been frozen were notviable when the cells were thawed.Clinical data regarding the 17 patients included in this studyare summarized in Table 2. The women ranged in age from 31to 55 years, with a mean age of 40 years. The implants had beenin place for an average of 3.7 years (range, 1.1 to 9 years). Allpatients presented with local complaints of either pain in thebreast or chest wall or capsular contracture. In addition, all ofthe patients subjectively reported one or more constitutionalcomplaints such as arthritis, myalgias, or chronic fatigue. Noneof the 17 patients in this study had well-documented specificrheumatologic diseases, and none had evidence of infection.Eleven patients had polyurethane-coated silicone gel breastimplants, and the remaining six had textured-surface siliconegel-containing breast implants (Table 2). Sixteen of the 17patients had bilateral breast implants.The samples analyzed by flow cytometry contained an averageof 4.5 3 106 cells (range, 0.5 3 106 to 15 3 106 cells). Thevolume of exudative fluid averaged around 1 to 3 ml. Stainedcytospin preparations from both the exudative fluids and capsularwashes revealed a predominance of lymphocytes (mean,62%) and macrophages (mean, 37%), with only a few segmentedneutrophils (mean, 2%).Flow cytometry. The immunophenotypic data regardingboth the implant-associated and peripheral blood lymphocytesare summarized in Tables 3 and 4, and representative contourplots are shown in Fig. 1 and 2. The vast majority of theimplant-associated lymphocytes were T cells (mean, 89%;range, 81 to 97%). The mean percentage of CD191 B cells wasonly 1.4% (range, 0.0 to 4.6%). A small percentage (mean,4.1%; range, 0.0 to 16%) of the implant-associated lymphocyteswere CD16/561 CD32 natural killer cells. Comparedwith the paired peripheral blood lymphocytes, the implantassociatedlymphocyte population had a significantly greaterproportion of T cells (P , 0.001) and significantly fewer B cells(P , 0.001) and natural killer cells (P , 0.001). In order tocompensate for this increased proportion of T cells, data regardingT-cell subsets were normalized on the basis of the totalpercentage of CD31 cells in order to provide a meaningfulTABLE 1. Antibody panel used in this studyCD (clone) Major specificity group FluorescentlabelDilutionSourceaCD45 (Hle-1) Pan-leukocyte FITC 1:1 BDCD14 (Leu-M3) Monocytes PE 1:1 BDCD3 (Leu-4) T cells FITC orPERCP1:1 BDCD4 (Leu-3) T-helper and/or inducercells, monocytesFITC orPERCP1:1 BDCD8 (Leu-2) T-cytotoxic and/orsuppressor cellsFITC 1:1 BDCD16/56 (Leu-11c 1 Leu-19)bNatural killer cells PE 1:1 BDCD19 (Leu-12) B cells PERCP 1:1 BDCD20 (Leu-16) B cells PERCP 1:1 BDCD29 (4B4) T-cell subset RD1 1:5 CICD45RO (2H4) T-cell subset RD1 1:64 CIHLA-DR PERCP 1:1 BDa BD, Becton Dickinson Immunocytometry Systems, San , Calif.; CI,Coulter Immunodiagnostics, Hialeah, Fla.b In a few cases, CD56 (Leu-19) was used alone.TABLE 2. Clinical data for the patients used in this studyAge(yr) Implant typea No. of yrwith implantReason forimplantb36 Meme (PU) 9 Rec41 Replicon (PU) 6 Rec35 Meme and Replicon (PU) 1.5 Rec, Aug35 Meme (PU) 2.4 Aug36 Meme (PU) 6 Aug55 Optimam (PU) 8 Rec41 Replicon (PU) 3 Aug46 Replicon (PU) 2.3 Aug34 Meme (PU) 7 Aug31 MSI (TS) 1.3 Rec45 Biocell (TS) 2.5 Aug40 Biocell (TS) 2 Rec47 Biocell (TS) 1.1 Aug51 Optimam and Meme (PU) 2.3 Rec37 Unknown (PU) 3.3 Aug39 Misty (TS) 1.4 Rec32 Mentor Siltex (TS) 2.5 Auga PU, polyurethane-coated silicone gel implant; TS, textured-surface Silasticimplant.b Rec, reconstruction; Aug, augmentation.VOL. 3, 1996 LYMPHOCYTES ASSOCIATED WITH SILICONE GEL IMPLANTS 157Downloaded from cvi.asm.org by on January 22, 2008comparison of these cell types between the two compartments.Among the implant-associated T cells, there was increasedexpression of HLA-DR (P , 0.001). Twenty-five percent of theCD31 cells coexpressed HLA-DR. There was a predominanceof CD41 T cells; for the implant-associated cells, the meanCD4/CD8 ratio was 1.8. Essentially all (greater than 99%) ofthe CD4 cells coexpressed CD29. Furthermore, almost all ofthe CD41 cells were negative for CD45RO. Compared withthe paired peripheral blood lymphocytes, the increase in CD41CD291 cells was marginally significant (P 5 0.043) and thedecrease in CD41 CD45RO1 cells was statistically significant(P , 0.001).The peripheral blood lymphocyte subsets in the patients withimplants were, in most respects, similar to those in healthycontrols (Table 5). These data are only preliminary, since thepatient and control populations were not matched with regardto sex or age. Nevertheless, the data do suggest that there is adecrease in the number of CD41 CD45RO1 cells in patientswith implants (P 5 0.022). Other differences in lymphocytesubsets did not appear to be statistically significant.DISCUSSIONDespite concern regarding possible immunologic abnormalitiesassociated with silicone gel breast implants, the phenotypeof implant-associated lymphocytes has not previously beenclearly defined. In preliminary studies, others have noted apredominance of T cells (29, 31). In this study, three-color flowcytometry was used to define the phenotypes of the lympho-FIG. 1. Representative contour plot of implant-associated lymphocytes stained with antibodies to CD4 and CD29 (4B4). The vast majority of the cells coexpressCD4 and CD29 (upper right quadrant).TABLE 3. Phenotype of implant-associated lymphocytes comparedwith that of paired peripheral blood lymphocytesPhenotype% of lymphocytes positiveaImplant Peripheral bloodCD31 (T cells) 89 6 4.9 71 6 9.1CD19 or CD201 (B cells)b 0.9 6 1.3 12 6 8.3CD16/561 CD32 (natural killer cells) 3.6 6 3.8 15 6 7.2a Values are means 6 standard deviations (n 5 16). For two-tailed probability,P , 0.001 (paired t test).b The B-lymphocytes in five of the peripheral blood samples were quantitatedwith antibodies to CD20 instead of CD19.TABLE 4. Implant-associated T-cell subsets compared with pairedperipheral blood T-cell subsetsPhenotype% of T cells positivea2-TailedprobabilitybImplant Peripheral bloodHLA-DR1 25 6 8.1 7.9 6 3.8 ,0.001CD41 CD291 68 6 12 59 6 13 0.043CD41 CD292 0.6 6 0.1 3.6 6 3.5 0.007CD41 CD45RO1 2.6 6 5.2 19 6 7.2 ,0.001CD41 CD45RO2 63 6 13 41 6 8.5 ,0.001CD81 37 6 10 42 6 9.6 0.115a Values are means 6 standard deviations (n 5 16).b Paired t test.158 KATZIN ET AL. CLIN. DIAGN. LAB. IMMUNOL.Downloaded from cvi.asm.org by on January 22, 2008cytes that are associated with polyurethane-coated and textured-surface silicone gel-containing breast implants. Thesetypes of implants were specifically chosen for this study becauseof the large number of lymphocytes that could be harvestedfrom the capsule or from the peri-implant fluid.Whether or not the inclusion of only textured-surface andpolyurethane-coated implants in our study introduced somebias cannot be determined from our available data. In all cases,there was a striking predominance of T cells. Most of the Tcells had the phenotype CD31 CD41 CD291 CD45RO2. Furthermore,among the T cells there was significant expression ofHLA-DR. Comparison of the implant-associated lymphocyteswith patient-matched peripheral blood lymphocytes, obtainedat the time of surgery, showed that the increase in CD31 cells,the increased expression of HLA-DR by the T cells, and thedecrease in expression of CD45RO by the CD41 cells were allstatistically significant (P , 0.001 for each comparison). Theincrease in the percentage of CD41 CD291 T cells among theimplant-associated lymphocytes compared with the level of thematched peripheral blood lymphocytes was of borderline statisticalsignificance (P 5 0.043).The role of textured-surface implants in eliciting an exudativehost response is uncertain. It is known that textured-surfaceSilastic implants, as well as polyurethane-covered implants,are frequently associated with synovial metaplasia ofthe lining of the fibrous capsule (30). Review of histologicsections from the capsules from each of the patients in thisstudy confirmed the presence of synovial metaplasia in allcases. In addition, in most capsules there was a marked lymphocyticinfiltrate together with foamy macrophages.The significance of the predominance of CD291 CD41 Tcells among the implant-associated lymphocytes is uncertain.CD41 T cells can generally be divided into two major functionalcategories. CD41 CD291 T cells proliferate maximallyto soluble antigen and increase antigen-specific antibody production(22). In contrast, CD41 CD45RO1 T cells induce CD8FIG. 2. Representative contour plot of peripheral blood lymphocytes stained with antibodies to CD4 and CD45RO (2H4). A significant fraction of the CD41 cellscoexpress CD45RO (upper right quadrant). PerCP, PERCP.TABLE 5. Patient peripheral blood lymphocytes compared withcontrol peripheral lymphocytesPhenotype% of lymphocytes positivea2-TailedImplant patients probabilityb(n 5 16)Controls(n 5 12)CD3 71 6 9.1 75 6 3.5 0.072CD31 HLA-DR1 5.5 6 2.5 3.9 6 2.3 0.097CD41 CD291 41 6 10 45 6 9.2 0.301CD41 CD45RO1 13 6 5.5 21 6 9.8 0.022CD81 30 6 7.6 25 6 7.1 0.081CD191 (or CD201)c 12 6 8.3 15 6 4.1 0.186CD16/561 CD32 15 6 7.2 11 6 5.0 0.069a Values are means 6 standard deviations.b Unpaired t test.c B lymphocytes in five of the patient peripheral blood samples were quantitatedwith antibodies to CD20 instead of CD19.VOL. 3, 1996 LYMPHOCYTES ASSOCIATED WITH SILICONE GEL IMPLANTS 159Downloaded from cvi.asm.org by on January 22, 2008cells to exert suppressor function (23). It is of interest thatCD41 CD291 T cells are also the predominant lymphocytesubset in synovial fluid of patients with rheumatoid arthritis(24). Furthermore, as we found for implant-associated lymphocytes,synovial tissue lymphocytes in patients with rheumatoidarthritis have increased expression of HLA-DR antigens (8).The apparent depletion of CD41 CD45RO1 T cells from theperipheral blood of patients with silicone gel-containing breastimplants will require confirmation by more extensive controlledstudies.To date, there is very little information that sheds light onthe manner whereby silicone gel-containing breast implantscould potentially cause connective tissue diseases. Some authorshave suggested that silicone or silicone-protein complexesmay themselves be antigenic (13, 18, 19, 44). Othershave drawn attention to the fact that a significant percentage ofwomen with silicone breast implants have antinuclear antibodies(5, 28). The results from animal studies have been conflicting(4, 25). Clinical studies of patients with silicone gel breastimplants suffer from the fact that patients are often referredbecause of symptoms of rheumatic disease. Large populationbasedepidemiologic studies are limited by the fact that ‘‘diseases’’potentially caused by silicone gel-containing implantshave not been clearly defined. Most of the patients in this studyreported a symptom complex similar to fibromyalgia. A preliminarystudy of 144 patients with breast implants also reportedclinical manifestations characteristic of fibromyalgia(45). Certainly there is no reproducibly specific marker forpatients with silicone gel-associated rheumatic disease. In onestudy, which has yet to be substantiated, Vasey and colleaguesreported clinical observations suggesting that rheumatic diseasesymptoms in patients with silicone gel implants may bereversible after implant removal (43). This finding should atleast provide the impetus for continued studies of the immunologiceffects of silicone.There are several inherent limitations in our study regardingits ability to address the questionable relationship betweensilicone breast implants and immunologic diseases. First, ourpatient population includes only those patients who are currentlyhaving problems with their implants. Because it is difficultto form a control group of patients with no local or systemicproblems and who wish to undergo implant removal andcapsulectomy, this study does not resolve the question ofwhether T-cell activation around polyurethane or texturedsurfacebreast implants is in fact a pathologic phenomenon.Although polyurethane-covered implants have been known toelicit greater inflammatory responses in the capsule thansmooth-shell implants, it is not clear from previous studieswhat type of inflammation they elicit (16). Nor is it clear fromprevious studies how long the inflammatory responses persist.Our study has shown that T-cell activation around these implantsoccurs as early as 1 year after implantation and canpersist for as long as 9 years.The other unresolved question which this study could notaddress is the significance of local T-cell activation in elicitinglocal pain and systemic illness. Although all patients studiedhad significant pain around their implants and all of the patientshad some concomitant constitutional symptoms, withouta large symptom-free control group, the effect of local T-cellactivation on the systemic immune system remains elusive.In summary, this study is the first to define the phenotype ofthe lymphocytes isolated from the fluid or tissue surroundingsilicone gel-containing breast implants. The lymphocytes arealmost all CD31 T cells, most of which express CD4 and CD29.Compared with peripheral blood lymphocytes, the T cells havesignificantly increased expression of HLA-DR and significantlyreduced expression of CD45RO. Histologic examination ofcapsular tissue, as well as examination of the exudative fluid,has shown that most of the implant-associated lymphocytes arepresent in association with foamy macrophages that are knownto ingest droplets of silicone gel. We have found that thesemacrophages strongly and uniformly express HLA-DR (17).Our results are consistent with the hypothesis that the siliconecontainingmacrophages act as antigen-presenting cells to CD4cells which become activated and subsequently function toup-regulate an immune response, as indicated by expression ofCD29. Admittedly, this simplistic hypothesis requires extensivefurther testing and refinement. In particular, it will be importantto determine whether the implant-associated CD41 Tcells belong to the Th1 or Th2 subset. A recent study byOjo-Amaize et al. (26) provides additional evidence in supportof the central role of T cells in the immunologic reaction tosilicone breast implants. In any case, if science is to prevail inthe silicone controversy, as Fisher rightly insists (10), thenfurther analysis of the inflammatory reaction to silicone breastimplants will be necessary.ACKNOWLEDGMENTSThis research was supported in part by a grant from the Haas Fund,The Mount Sinai Medical Center, Cleveland, Ohio.We express our gratitude to Hom of the Department ofEpidemiology and Biostatistics at Case Western Reserve UniversitySchool of Medicine, Cleveland, Ohio, for assistance with the statisticalanalyses.REFERENCES1. Baker, J. L., R. R. LeVier, and D. E. Spielvogel. 1982. Positive identificationof silicone in human mammary capsular tissue. Plast. Reconstr. Surg. 69:56–60.2. Baldwin, C. 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Bocanegra. 1994.Clinical manifestations in 144 patients with breast implants (BI). A comparisonwith primary fibromyalgia (PFM). Arthritis Rheum. 36(Suppl.):R28.(Abstract.)46. Weiner, S. R., and H. E. us. 1986. Chronic arthropathy occurring afteraugmentation mammaplasty. Plast. Reconstr. Surg. 77:185–187.47. Weisman, M. H., T. R. Vecchione, D. Albert, L. T. , and M. R. Mueller.1988. Connective-tissue disease following breast augmentation: a preliminarytest of the human adjuvant disease hypothesis. Plast. Reconstr. Surg.82:626–630.VOL. 3, 1996 LYMPHOCYTES ASSOCIATED WITH SILICONE GEL IMPLANTS 161Downloaded from cvi.asm.org by on January 22, 2008Effect of silicone on macrophages:

The effect of silicones on the immune function is not fully characterized.In clinical and experimental studies, immune alterations associated withsilicone gel seem to be related to macrophage activation. In this work weexamined in vivo, phenotypic and functional changes on peritonealmacrophages early (24 h or 48 h) and late (45 days) after theintraperitoneal (i.p.) injection of dimethylpolysiloxane (DMPS) (silicone).We studied the expression of adhesion and co-stimulatory molecules and boththe spontaneous and the stimulated production of reactive oxygenintermediates and nitric oxide (NO). ResultsThe results presented here demonstrate that the fluid compound DMPS induceda persistent cell recruitment at the site of the injection. Besides, cellactivation was still evident 45 days after the silicone injection: activatedmacrophages exhibited an increased expression of adhesion (CD54 and CD44)and co-stimulatory molecules (CD86) and an enhanced production of oxidantmetabolites and NO. ConclusionsSilicones induced a persistent recruitment of leukocytes at the site of theinjection and macrophage activation was still evident 45 days after theinjection. Create a Home Theater Like the Pros. Watch the video on AOL Home.