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ID PMID Title PublicationDate abstract
8163935 Immunoregulatory role of interleukin 10 in rheumatoid arthritis. 1994 May 1 The presence and the role of interleukin 10 (IL-10), a potent cytokine synthesis inhibitory factor and antiinflammatory cytokine, were investigated in rheumatoid arthritis (RA). The expression of both mRNA and protein for IL-10 could be demonstrated in RA and osteoarthritis (OA) joints. Human IL-10 mRNA could be demonstrated by polymerase chain reaction amplification of cDNA made by reverse transcription of total RNA extracted directly from synovial tissue in five out of five RA and four out of five OA patients. IL-10 protein was demonstrated by specific immunoassay and immunohistology. IL-10 protein was spontaneously produced in all 11 RA and 17 OA synovial membrane cultures investigated, and this production was sustained for up to 5 d in culture in the absence of any extrinsic stimulation. IL-10 protein could also be detected by immunohistology in all five RA and four OA synovial membrane biopsies investigated, but not three normal synovial membranes. Immunohistology revealed that the IL-10 was localized to the synovial membrane lining layer and mononuclear cell aggregates. Immunofluorescence double staining revealed that the sources of IL-10 were monocytes in the lining layer, and T cells in the mononuclear cell aggregates. We found evidence that the IL-10 expression was functionally relevant, as neutralization of endogenously produced IL-10 in the RA synovial membrane cultures resulted in a two- to threefold increase in the protein levels of proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and IL-1 beta, although IL-6 and IL-8 levels were not affected. The addition of exogenous recombinant IL-10 to the RA synovial membrane cultures resulted in a two- to threefold decrease in the levels of TNF-alpha and IL-1 beta. IL-8 levels were reduced by day 5; however, IL-6 levels were not affected by exogenous IL-10. Neutralization of the endogenous IL-10 in two out of seven RA synovial membrane cultures resulted in the expression of detectable levels of interferon gamma (561-1,050 pg/ml). Taken together, the above findings suggest that IL-10 is spontaneously produced in RA and OA and is an important immunoregulatory component in the cytokine network of RA, regulating monocyte and in some cases T cell cytokine production.
1354228 Diseases of the intestine mimicking Crohn's disease. 1992 Jul We describe five patients who were initially thought to have Crohn's disease and were treated accordingly. The original diagnosis was based upon clinical presentation, roentgenograms, and histological examination, but subsequent follow-up showed that diagnosis to be in error. The following diagnoses were established instead: tuberculosis, Actinomyces Israeli infection, reaction to gold therapy, metastatic cancer, and linitis plastica. We stress the importance of considering conditions that can mimic Crohn's disease.
7509510 Detection of antiphospholipid antibodies by flow cytometry: rapid detection of antibody is 1993 Oct 18 Laboratory diagnosis of antiphospholipid antibodies is important in patients with clinical features of the antiphospholipid syndrome, such as thrombosis and fetal loss. We have developed a novel method for the detection of antiphospholipid antibodies using flow cytometry. Anionic phospholipids cardiolipin, phosphatidylserine and phosphatidylinositol are coated onto polystyrene beads of different sizes, allowing detection and semiquantitation of their respective phospholipid antibody isotypes. The results of the flow cytometric method closely correlate those of the standardised anticardiolipin enzyme-linked immunosorbent assay (ELISA), but the method is quicker and is versatile in its ability to detect IgG, IgM and IgA antibody isotypes at the same time. The method promises to be useful in evaluating the significance of phospholipid specificity and antibody isotypes in patients with the antiphospholipid syndrome.
8256163 [Clinical study of Still's disease as a distinct disease entity]. 1993 Oct There seems to be yet unresolved questions as to whether child-onset and adult-onset Still's disease are truly the same disease and whether adult-onset Still's disease is a disease entity independent of other rheumatic diseases in the adult. In order to clarify these issues, we have analyzed statistically the clinical features of Still's disease of various age-onset and also compared the features of adult-onset Still's disease with those of other rheumatic diseases having similar manifestations. Clinical data used for the study were those collected from 32 institutions in Japan through questionnaire method by Adult Still's Disease Research Committee, and the patients with adult Still's disease and with other rheumatic diseases were definitely diagnosed by the Committee. When the sensitivity of each of total 90 clinical items was compared between child-onset adult Still's disease (11 cases) and adult-onset Still's disease (77 cases), and between young adult-onset (16-35 years) Still's disease (48 cases) and aged adult-onset (45 years or older) Still's disease (15 cases), only 7-9% of the items showed significant difference by chi 2-test. This was the same range as when the sensitivity of the clinical items obtained from the literature of child-onset Still's disease (26 cases) was compared with that of adult-onset Still's disease (77 cases). On contrary to this range, over half of the items showed the significant difference in sensitivity when adult-onset Still's disease was compared with other rheumatic diseases such as seronegative rheumatoid arthritis (31 cases), malignant rheumatoid arthritis (25 cases), and polyarteritis nodosa (31 cases).(ABSTRACT TRUNCATED AT 250 WORDS)
7923425 [Tuberculous infection and autoimmune diseases]. 1993 Oct This paper presented four cases to demonstrate the close relationship between tuberculosis and autoimmune diseases. The patients had clinical manifestation of autoimmune diseases with presence of anti-PPD IgG, specific circulating immune complexes in sera. After being treated with antituberculous chemotherapy, all patients got distinct improvement clinically. Also, the possible mechanisms of their correlationship were reviewed and discussed.
1532804 Increase in TCR gamma delta T lymphocytes in synovia from rheumatoid arthritis patients wi 1992 Mar To determine the relative presence of TCR gamma delta+ and TCR alpha beta+ T cells in synovial tissue from patients with various types of inflammatory synovitis and in tissues from patients with a number of chronic T cell-mediated conditions, we stained frozen tissue sections with monoclonal antibodies in indirect immunofluorescence assays. In tissues obtained from patients with chronic T cell-mediated granulomatous conditions (Wegener's granulomatosis, lymphomatoid granulomatosis, granuloma annulare, Langerhans' cells granulomatosis, pigmented villonodular synovitis, Takayasu's arteritis, and talc granulomatosis), the T cells present were predominantly TCR alpha beta+, without an increased presence of TCR gamma delta+ cells. In contrast, 6 of 14 (43%) synovia from patients with rheumatoid arthritis (RA) showed increased TCR gamma delta+ T cells (3-10 cells/hpf). The RA synovia with increased TCR gamma delta+ cells present had an increased tissue inflammation score compared to RA synovia with few TCR gamma delta+ cells [18.6 +/- 5.8 versus 11.6 +/- 4.2 (mean +/- SE), P less than 0.05]. In contrast, synovia from patients with osteoarthritis, systemic lupus erythematosus, and trauma did not show an increased presence of TCR gamma delta+ T cells. Thus, in cellular inflammatory infiltrates the presence of increased TCR gamma delta cells is not a component of noninfectious granulomatous inflammation but is found in approximately 40% of RA synovia with high levels of inflammation.
1371126 Selective induction of rheumatoid factors by superantigens and human helper T cells. 1992 Feb Production of autoantibodies specific for the Fc region of autologous IgG, called rheumatoid factors (RF), is a characteristic finding in patients with rheumatoid arthritis (RA). To study the requirements regulating the synthesis of these autoantibodies, we have cloned human helper T cells and co-cultured them with purified B cells. To mimic cognate T-B cell interaction, we have used bacterial superantigens that function by cross-linking HLA molecules on the B cell with selected T cell receptor (TCR) molecules expressing a particular polymorphism of the V beta gene segment. Data presented here demonstrate that the staphylococcal enterotoxin D (SE D), but not other bacterial superantigens, exhibits an ability to induce IgM, IgG, and especially RF production, in B cells from RA patients and normal individuals. Comparison with the polyclonal antibody production in B cell cultures driven by anti-CD3-stimulated T cell clones confirmed that SE D shifted the repertoire of secreted antibodies toward immunoglobulins with Fc binding specificity, suggesting that SE D preferentially stimulates RF+ B lymphocytes. B cells with the potential to secrete RF were highly frequent in RA patients, requiring as few as 150 peripheral B cells/culture to detect RF in the culture supernatants. SE D-induced RF synthesis was strictly dependent on the presence of selected CD4+T helper cells and required a direct membrane contact between B cells and T helper cells. Here, we propose a model that SE D selectively induces RF production depending on the availability of SE D responsive T cells in the TCR repertoire of the responder.
8850166 A solid-phase antibody capture assay for the measurement of C1-inhibitor consumption in vi 1996 Feb C1-inhibitor (C1-Inh) is a serine esterase proteinase inhibitor (serpin) which plays an important role in regulating serine proteinases of the early inflammatory response. In this study, we describe a novel and versatile polyclonal antibody capture assay to examine C1-Inh consumption in vivo. This assay has advantages over previously described methods of measuring C1-Inh consumption as it allows the assessment of the relative amounts of native, complexed and cleaved inhibitor circulating in plasma. By using polyclonal antibodies specific for other complement proteins, the C1-Inh capture assay was adapted to measure in vivo activation of C3, C4 and factor B. C1-Inh consumption and complement activation were examined in the plasma of 21 normal individuals, 24 individuals with systemic lupus erythematosus (SLE), nine individuals with adult respiratory distress syndrome (ARDS) and in the paired plasma and synovial fluid from 18 patients with rheumatoid arthritis (RA). The C1-Inh capture assay revealed native, cleaved and complexed C1-Inh migrating at 115 kDa, 96 kDa and 209-225 kDa respectively, in normal plasma. C1-Inh consumption was increased in the plasma of all the inflammatory disorders examined, in comparison to normal plasma. It is proposed that this serpin capture assay could be adapted to the study of serpin involvement in a wide variety of inflammatory disorders.
1334331 Modulation of kinin responses in human synovium by interleukin-1. 1992 Bradykinin (BK) is a weak stimulus for prostaglandin E2 (PGE2) release in untreated human synovial cells, but a potent stimulus in interleukin-1 (IL-1) pretreated cells. The mechanism(s) by which IL-1 induces responsiveness of synovial cells to BK appears to be multifactorial. IL-1 not only upregulates the number of kinin receptors on these cells, but may also upregulate a calcium-dependent process involved in the synthesis of prostaglandins.
8898940 Prevention and amelioration of collagen-induced arthritis by blockade of the CD28 co-stimu 1996 Oct Collagen type II-induced arthritis (CIA) is an experimental model of arthritis that has been successfully used to dissect the pathogenesis of human rheumatoid arthritis and to identify potential therapeutic targets. We have used this model to evaluate the role of T cell co-stimulation in both disease development and progression. T cell co-stimulation is provided by ligation of CD28 with either B7-1 or B7-2 present on antigen-presenting cells and can be prevented by a soluble form of CTLA-4 (CTLA-4Ig) which binds with high affinity to both B7-1 and B7-2. We found that administration of CTLA-4Ig at the time of immunization prevented the development of CIA and was associated with lack of lymphocyte expansion within the draining lymph node and failure to produce anti-collagen IgG1 or IgG2a antibodies. To determine which CD28 ligand plays a more dominant role in CIA, we treated mice with monoclonal antibodies (mAb) against either B7-1 or B7-2. Neither anti-B7-1 nor anti-B7-2 had any effect on the course of CIA when given alone, but resulted in reduced incidence and clinical scores when given together. Interestingly, when treatment was delayed until after the onset of clinical disease, both CTLA-4Ig or anti-B7-1 plus anti-B7-2 mAb still ameliorated disease. Effective treatment was associated with a reduction in interferon-gamma production by lymph node cells following stimulation in vitro, suggesting that Th1 responses were diminished. This study points to a critical role of CD28 co-stimulation in the development and perpetuation of CIA in DBA/1 mice. Interestingly, it demonstrates an active role for T cells in the later stages of this disease and implicates both B7-1 and B7-2-mediated co-stimulation in the pathogenesis of CIA.
7826140 Increased serum proMMP-3 in inflammatory arthritides: a potential indicator of synovial in 1994 Nov OBJECTIVE: To investigate if the increased concentrations of stromelysin (MMP-3) found in the synovial fluid (SF) of patients with various arthritides reflect the concentrations in the circulation. METHODS: Using a double antibody ELISA, we have measured proMMP-3 concentrations in sera from these patient groups and in others with a heightened acute phase response (APR) as a result of multiple organ failure. RESULTS: The median serum concentration of proMMP-3 was increased by up to ninefold in the inflammatory arthritides, but not in osteoarthritis or in patients with a heightened APR resulting from a non-chronic inflammatory condition. CONCLUSION: In chronic inflammatory diseases such as rheumatoid arthritis, serum proMMP-3 may prove to be a more specific indicator of monokine activity than currently available serum markers.
8300888 Ketoprofen pharmacokinetics in the elderly: influence of rheumatic disease, renal function 1993 Nov An age-related accumulation of ketoprofen due to a reduced clearance has been reported in the elderly. Other studies have not observed these changes in the kinetics of unchanged ketoprofen, but have reported increased plasma levels and reduced urinary excretion of conjugated ketoprofen. The authors examined the effects of dose, renal function, and the presence of arthritis on the stereoselective kinetics of ketoprofen in five nonarthritic and six arthritic elderly subjects. There was a significant difference in renal function (CLCr, mL/min; arthritic, 71.8 +/- 12.3, nonarthritic, 91.4 +/- 11.1), but not in age or weight between the two groups. Subjects received 50 mg and then 150 mg enteric-coated racemic ketoprofen, and plasma and urine samples were collected for 24 hours. No significant differences in CL/F, area under the curve (AUC), half-life (t1/2), time to reach peak concentration (tmax), or maximum peak plasma concentration (Cmax) were found between groups or between doses, and values were similar to those previously reported in young adults. Urinary ketoprofen conjugate (S:R) ratio was 1.6 +/- .25 and 1.65 +/- .27 for arthritic and nonarthritic subjects. Greater amounts of conjugated ketoprofen enantiomers were present in the plasma of the arthritic compared with nonarthritic subjects. Renal clearance of ketoprofen conjugates exhibited stereoselectivity (R > S), and was decreased in the arthritic group. Significant changes in the kinetics of unchanged ketoprofen was not found to occur in elderly subjects in the presence or absence of rheumatic disease or moderate renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS)
8478378 Capitellocondylar total elbow replacement in rheumatoid arthritis. Long-term results. 1993 Apr We evaluated the long-term results of 202 capitellocondylar total elbow replacements that had been performed, from July 1974 through June 1987, in 172 patients. The duration of follow-up averaged sixty-nine months (range, twenty-four to 178 months). At the most recent follow-up examination, use of a 100-point rating score demonstrated an improvement from an average preoperative score of 26 points (range, 2 to 50 points) to an average postoperative score of 91 points (range, 45 to 100 points). The most improvement occurred in the categories of relief of pain, functional status, and range of motion in all planes except extension. The improvements in these categories and in the roentgenographic appearance that were seen in the early postoperative period did not deteriorate with time. The average preoperative arc of motion at the elbow ranged from -37 degrees of extension to 118 degrees of flexion. The average postoperative arc of motion at the elbow ranged from -30 degrees of extension to 135 degrees of flexion. Supination improved from 45 degrees preoperatively to 64 degrees postoperatively; pronation improved from 56 degrees preoperatively to 72 degrees postoperatively. The roentgenograms showed a radiolucent line adjacent to eight humeral and nineteen ulnar components; most of the lines were incomplete and one millimeter wide or less. Revision of the prosthesis was necessary in three elbows (1.5 per cent) because of loosening without infection, and in three additional elbows because of dislocation of the prosthesis. Complications included deep infection in three elbows (1.5 per cent); problems related to the wound in fifteen (7 per cent); permanent, partial sensory ulnar-nerve palsy in five (2.5 per cent); permanent, partial motor ulnar-nerve palsy in one (0.5 per cent); and dislocation in seven (3.5 per cent).
8477124 Nabumetone: a "nonacidic" nonsteroidal antiinflammatory drug. 1993 Apr OBJECTIVE: To review the pharmacology, pharmacokinetic disposition, dosage recommendations, adverse effects, drug interactions, and efficacy of nabumetone in patients with selected rheumatic disorders and soft-tissue injuries. DATA SOURCES: Data from scientific literature were extracted, evaluated, and summarized for presentation. A MEDLINE search was conducted using the following indexing terms: antiinflammatory agents, nonsteroidal, nabumetone, rheumatoid arthritis (RA), and osteoarthritis (OA). Studies evaluating nabumetone reported in articles, abstracts, or proceedings involving human subjects were considered for inclusion. STUDY SELECTION: Special consideration was given to clinical studies using double-blind, randomized, parallel, controlled designs. Studies comparing the effectiveness and safety of nabumetone with placebo and other nonsteroidal antiinflammatory drugs (NSAIDs) were included. DATA EXTRACTION: Data from human studies published in the English language were evaluated. Trials were assessed according to study design, sample size, and description of outcomes. DATA SYNTHESIS: Nabumetone is a nonacidic prodrug that is metabolized to an active nonsteroidal antiinflammatory moiety, 6-methoxy-2-naphthylacetic acid (6-MNA). 6-MNA is a structural analog of naproxen. Like naproxen and other NSAIDs, 6-MNA possesses analgesic, antipyretic, and antiinflammatory activity, 6-MNA has a prolonged elimination half-life, ranging from 17 to 74 hours, which allows for once-daily dosing. The efficacy of nabumetone for treating symptoms of RA and OA has been established in controlled clinical trials. Nabumetone also has been studied in ankylosing spondylitis and soft-tissue injuries. Adverse effects associated with nabumetone are similar to those associated with other NSAIDs. Gastrointestinal reactions occur most frequently in the form of abdominal pain or indigestion, nausea, or vomiting. Central nervous system adverse effects occur less frequently, and are followed in order of occurrence by rashes. CONCLUSIONS: Nabumetone is a prodrug metabolized to an active metabolite structurally related to naproxen. Studies have demonstrated the efficacy of nabumetone, but no advantages over the many other NSAIDs now available.
8943052 A novel mechanism of action of tetracyclines: effects on nitric oxide synthases. 1996 Nov 26 Tetracyclines have recently been shown to have "chondroprotective" effects in inflammatory arthritides in animal models. Since nitric oxide (NO) is spontaneously released from human cartilage affected by osteoarthritis (OA) or rheumatoid arthritis in quantities sufficient to cause cartilage damage, we evaluated the effect of tetracyclines on the expression and function of human OA-affected nitric oxide synthase (OA-NOS) and rodent inducible NOS (iNOS). Among the tetracycline group of compounds, doxycycline > minocycline blocked and reversed both spontaneous and interleukin 1 beta-induced OA-NOS activity in ex vivo conditions. Similarly, minocycline > or = doxycycline inhibited both lipopolysaccharide- and interferon-gamma-stimulated iNOS in RAW 264.7 cells in vitro, as assessed by nitrite accumulation. Although both these enzyme isoforms could be inhibited by doxycycline and minocycline, their susceptibility to each of these drugs was distinct. Unlike acetylating agents or competitive inhibitors of L-arginine that directly inhibit the specific activity of NOS, doxycycline or minocycline has no significant effect on the specific activity of iNOS in cell-free extracts. The mechanism of action of these drugs on murine iNOS expression was found to be, at least in part, at the level of RNA expression and translation of the enzyme, which would account for the decreased iNOS protein and activity of the enzyme. Tetracyclines had no significant effect on the levels of mRNA for beta-actin and glyceraldehyde-3-phosphate dehydrogenase nor on levels of protein of beta-actin and cyclooxygenase 2 expression. These studies indicate that a novel mechanism of action of tetracyclines is to inhibit the expression of NOS. Since the overproduction of NO has been implicated in the pathogenesis of arthritis, as well as other inflammatory diseases, these observations suggest that tetracyclines should be evaluated as potential therapeutic modulators of NO for various pathological conditions.
8720271 [A case of rheumatoid arthritis associated with pernicious anemia and bronchiolitis oblite 1995 Dec A case of rheumateid arthritis (RA) with pernicious anemia (PA) and wandering multiple patchy densities in bilateral lung fields is reported. A 72-year-old woman was hospitalized in February 1994, because of cough. She had already advanced RA (Class IV, Stage IV). She showed macrocytic and hyperchromic anemia as follows ; red-cell count (RBC), 176 x 10(4)/microliters; hemoglobin (Hb),7.2 g/dl; hematocrit (Ht), 21.0% ; MCV, 119.3 fl; and MCH, 40.9 pg. Chest roentgenogram revealed multiple patchy densities in bilateral lung fields and there was no response to the administration of antibiotic agents. From these clinical pictures bronchiolitis obliterans organizing pneumonia (BOOP) was highly suspected. After steroid injection into the joint space, the abnormal lung shadows disappeared. Anemia had been recovering spontaneously, but recurred in July. The results of blood examination were as follows ; RBC, 162 x 10(4)/microliters; Hb, 6.7ng/dl; Ht, 19.1%; MCV, 117.9 fl; and MCH, 41.4 pg. Anti-intrinsic factor antibody was positive. The level of serum vitamin B12 was low, 76 pg/ml. Sternal bone marrow aspiration showed magaloblastic changes with hypersegmentation of granulocytes. PA was diagnosed and improvement was noted after the intramuscular administration of vitamin B12. Subjective symptoms based on RA did not change during the clinical course. It is suggested that the pathogenesis about the combination of RA, BOOP and PA is related to common immunological abnormalities in our patient. A case of RA with PA and BOOP has not been reported previously, thus this case is considered clinically valuable.
7944620 Submicroscopic crystals in osteoarthritic synovial fluids. 1994 Jul OBJECTIVES: To investigate the hypothesis that synovial fluid (SF) from patients with osteoarthritis (OA) may contain calcium phosphate crystals that are either too small, or too few in number to be identified by conventional light microscopy techniques. METHODS: Twelve SF from 11 patients with established knee OA, five SF from patients with rheumatoid arthritis (RA), and two control samples of SF from patients with pseudogout were subjected to an enzyme/hypochlorite extraction procedure. The patients with OA and RA had no radiographic evidence of chondrocalcinosis, or SF crystals on polarised light microscopy. Extracted material was examined and analysed by analytical electron microscopy (AEM) and x ray powder diffraction (XRD). RESULTS: Mineral was found in 11 of 12 OA samples, ranging from 2-120 micrograms/ml SF. Analytical electron microscopy revealed calcium pyrophosphate dihydrate (CPPD) crystals in five (confirmed by XRD in three) and basic calcium phosphates (BCP) in eight (five on XRD). Two samples with confirmed CPPD contained some rods with a mean length below 100 nm. The majority of BCP clusters were also less than 100 nm in diameter. BCP was detected in 1/5 RA samples. Control samples contained CPPD crystals of the expected size range of 0.42-17.9 microns. CONCLUSIONS: The data indicate that many OA SF may contain CPPD or BCP crystals which are too small or too few in number to be identified by conventional techniques. Crystal deposition is not an 'on-off' phenomenon in OA.
7561125 High avidity state of leukocyte function-associated antigen-1 on rheumatoid synovial fluid 1995 Oct 15 The integrin LFA-1 (CD11a/CD18) is a cell surface adhesion molecule required for leukocyte extravasation and subsequent immune and inflammatory responses. Rapid transition between nonadherent and adherent states of LFA-1 is of key importance to Ag-specific recognition of T lymphocytes. In this paper, LFA-1-mediated adhesiveness of peripheral blood (PB) and synovial fluid (SF) T lymphocytes to affinity-purified ICAM-1-coated plates was studied in patients with rheumatoid arthritis (RA) and in patients with non-RA panels, including osteoarthritis, ankylosing spondylitis, erythema nodosum, pseudogout, and pustulosis. LFA-1-mediated adhesiveness of SF T lymphocytes was not observed in any of the 10 non-RA patients studied, although cross-linking of the TCR on lymphocytes from these patients rapidly converted LFA-1 to an adhesive state. In contrast, SF T lymphocytes from 10 of 12 RA patients exhibited LFA-1-mediated adhesiveness without a requirement for cross-linking of the TCR. No difference was seen in the cell surface density of LFA-1 between non-RA and RA T lymphocytes, suggesting that the difference in adhesiveness was due to a high avidity state of LFA-1 on SF T lymphocytes in RA. Furthermore, exposure of PB T lymphocytes, which showed a low avidity state of LFA-1, to whole SF from RA patients that was depleted of T lymphocytes could induce a high avidity state of LFA-1 in vitro. Cellfree SF from RA patients also could stimulate adhesiveness, although to a lesser extent. These data suggest the existence of a LFA-1-activating environment that is selectively found in SF from RA patients.
8870693 Mononuclear cell retention in rheumatoid synovial tissue engrafted in severe combined immu 1996 Oct The aim of this study was to assess regulation of mononuclear cell (MNC) traffic to human synovial tissue by TNF-alpha and IL-1 and the involvement of ICAM-1 in MNC retention in rheumatoid synovial tissue. Human rheumatoid arthritis synovium was engrafted subcutaneously in 6-8 week-old SCID/CB17 mice. Three weeks later, we injected 20 x 10(6) human peripheral blood mononuclear cells (PBMC) previously labelled with 111indium intraperitoneally into mice containing control or cytokine-injected grafts. Total body scintigraphy was performed 72 h postinjection. The graft was removed and immunochemical analysis carried out to assess ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression. In some experiments, mice were treated intravenously with 500 micrograms MoAb anti-ICAM-1 (BIRR-1) or an isotype-matched control MoAb before introduction of MNC. TNF-alpha, but not IL-1 alpha, enhanced MNC retention in the rheumatoid synovial graft 72 h post-injection (graft activity 989 +/- 1227 ct/min per 200 pixels or 3.36 +/- 4.16% of initial injected activity versus 411 +/- 157 ct/min per 200 pixels or 1.13 +/- 0.45% in controls; P < 0.03). TNF-alpha enhanced ICAM-1 expression by synovial cells and endothelial cells, whereas VCAM-1 or E-selectin expression was not enhanced on either cell type. After MoAb treatment of ICAM-1, synovial lymphocyte recruitment of TNF-alpha-treated mice decreased significantly to levels below that of control mice (160 +/- 97 ct/min per 200 pixels, 0.54 +/- 0.33%; P < 0.01). Mononuclear cell retention in rheumatoid synovial tissue engrafted into SCID mice was up-regulated by TNF-alpha and blocked by MoAb to ICAM-1. These results suggest that ICAM-1 is involved in mononuclear cell retention in rheumatoid synovium.
1281201 Human bone marrow stromal cell lines from myeloma and rheumatoid arthritis that can suppor 1992 Dec 15 In order to elucidate the pathologic significance of the bone marrow (BM) microenvironment in multiple myeloma (MM) and rheumatoid arthritis (RA), we established patient- or healthy donor (HD)-derived BM stromal cell lines by transfecting the plasmid for expression of SV40 large T Ag and examined their ability to support the stromal cell-dependent growth of a pre-B cell line, DW34. The means of recovered cell numbers of DW34 co-cultured with MM- and RA-derived BM stromal cell lines ranged from 6- to 10-fold more than those with HD-derived ones. Their enhanced ability to support DW34 cell growth was not caused by cytokines, including IL-6, IL-7, and c-kit ligand, although exogenous IL-7 could augment the growth-supporting ability. DW34 cell growth on the stromal cell lines was abolished by inhibiting cell-to-cell interaction with a membrane filter. FACS analysis revealed that the stromal cell lines did not express LFA-1 alpha, beta, NCAM, or ELAM-1. Both patient and HD BM stromal cell lines variably expressed ICAM-1, VCAM-1, and CD44. However, surface expression levels of these molecules did not correlate with the ability of the stromal cell lines to support DW34 cell growth. Taken together, these results suggested that BM microenvironment might play important roles in the pathogenesis of MM and RA.