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ID PMID Title PublicationDate abstract
22806136 Osteoconductive action of alendronate after implantation of beta tricalcium phosphate in r 2012 Nov The aim of the study was to determine the effect of alendronate on resorption of β-tricalcium phosphate (β-TCP) and bone formation in rats with adjuvant-induced arthritis (AIA). After preparation of a model of AIA in rats (day 0), alendronate or vehicle was injected intraperitoneally once daily five times in a week. Cylindrical β-TCP was implanted into the rat femoral condyle on day 7. Rats were killed on days 12, 15, and 21, and specimens and serum samples were collected. Specimens were analyzed by tartrate-resistant acid phosphate (TRAP) staining, immunohistochemistry of the ED1 protein, and in situ hybridization with digoxigenin-labeled α1 chain of type I procollagen (COL1A1). Mineralized bone sections were analyzed by Villanueva bone stain. The serum osteocalcin level was measured using an enzyme-linked immunosorbent assay kit. Alendronate decreased the number of TRAP-positive cells attached to β-TCP, the numbers of ED1-positive multinucleated giant cells, and resorption of β-TCP. In AIA rats treated with alendronate, COL1A1 mRNA-positive cells adhered to β-TCP were round or cuboid whereas the cells in untreated AIA rats were fibroblast-like cells. Alendronate increased calcification of newly formed bone whereas it did not restore the bone formation suppressed with inflammation. These results suggest that alendronate has the potential to conduct mature bone after implantation of β-TCP in AIA. Alendronate may help to reduce insufficiency of newly formed bone after implantation of β-TCP in diseases characterized by increased bone resorption such as rheumatoid arthritis.
22178199 Primary biliary cirrhosis and Sjögren's syndrome: autoimmune epithelitis. 2012 Aug Primary biliary cirrhosis (PBC) has been often coined a model autoimmune disease based on the homogeneity amongst patients, the frequency and similarity of antimitochondrial antibodies, including the highly directed immune response to pyruvate dehydrogenase (PDC-E2). A significant number of patients with PBC suffer from sicca and amongst these, there are patients who also have classic Sjögren's syndrome. Indeed, both PBC and Sjögren's syndrome are characterized by inflammation of target epithelial elements. Both diseases can be considered on the basis of a number of other related clinical aspects, including proposed unique apoptotic features of the target tissue, the role of secretory IgA, and the frequency with which both diseases overlap with each other. Indeed, PBC may be considered a Sjögren's syndrome of the liver, whereas Sjögren's syndrome can be equally discussed as PBC of the salivary glands. Dissection of the genetic predispositions for both diseases and especially the molecular basis of effector mechanisms, will become critical elements in developing new therapies.
21820608 Genetic susceptibility to juvenile idiopathic arthritis in Iranian children. 2011 May BACKGROUND AND AIMS: This study was comprised of Iranian children with oligoarthritis and rheumatoid factor negative (RF) polyarthritis subtypes of juvenile idiopathic arthritis (JIA) to determine the association of HLA-DRB1 alleles in Iran. METHODS: HLA-DRB1 alleles were investigated in 33 Iranian children with oligoarthritis and RF negative polyarthritis JIA and compared with 45 healthy controls. HLA typing was performed by PCR with sequence specific primers in either of the two groups and followed by direct detection of HLA polymorphism by sequence analysis in patient group. RESULTS: HLA-DRB1*11 was found to be the most frequent allele associated with oligoarthritis and RF negative polyarthritis JIA in Iran followed by HLA-DRB1*8. The frequencies of HLA-DRB1*04 and *13 were not significantly different in both groups. CONCLUSIONS: We concluded that there was a significant difference in allele frequencies between patients and control group that may help in predicting the susceptibility to oligoarthritis and rheumatic factor negative polyarthritis JIA.
22651805 The relationship between hand osteoarthritis and serum leptin concentration in participant 2012 May 31 INTRODUCTION: Leptin has been suspected to contribute to the development of osteoarthritis (OA). However, this hypothesis has not been tested in large-scale hand OA cohorts. Our study aimed to determine whether there is a cross-sectional relationship between serum leptin levels and hand OA in a population-based sample of US adults. METHOD: We used the Third National Health and Nutrition Examination Survey (NHANES III), a national cross-sectional population-based survey, to study the relationship between hand OA and serum leptin concentration. We applied previously established classification criteria for hand OA. Patients with rheumatoid arthritis were excluded. Potential confounders included sex, body mass index, the presence of polyarticular OA, diabetes, and total cholesterol. We estimated unadjusted mean leptin concentration by hand OA status and by all confounders. We further developed a linear regression model to assess mean leptin levels, adjusted for appropriate confounders. RESULTS: Of 2,477 subjects in the NHANES III sample that had a hand examination and did not have rheumatoid arthritis, 1,056 (42.6%) had a leptin measurement and were included in the analysis. Subjects with and without leptin measurement had similar demographic characteristics. We did not find any significant differences in mean serum leptin levels in subjects with symptomatic hand OA (7.38 ng/ml in males (95% confidence interval (CI) = 5.31, 9.46) and 21.55 ng/ml in females (95% CI = 17.08, 26.02)), asymptomatic hand OA (6.69 ng/ml in males (95% CI = 5.19, 8.18) and 17.09 ng/ml in females (95% CI = 15.00, 19.18)), and no hand OA (8.22 ng/ml in males (95% CI = 7.47, 8.97) and 20.77 ng/ml in females (95% CI = 18.01, 23.53)) in the unadjusted analysis. In a multivariable linear regression model that included variables of hand OA status, age, race/ethnicity, and obesity status, we found no statistically significant association between serum leptin and hand OA status. CONCLUSIONS: In this cross-sectional study of a large representative US cohort, we did not find any evidence to support the hypothesis that serum leptin is associated with hand OA.
22286813 Single-dose and steady state pharmacokinetics of CSA and two main primary metabolites, AM1 2011 Sep BACKGROUND: Cyclosporine A (CsA) is an immunomodulatory agent used in standard immunosuppressive regimens in solid organ transplantations as well as in the treatment of autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus and psoriasis. Its immunosuppressive activity is primarily due to parent drug. However, following oral administration, absorption is incomplete and varies between individuals. Further, there is a dearth of pharmacokinetic data for CsA in autoimmune patients compared to transplant recipients. AIM: The goal of this study was to investigate the single-dose and steady state pharmacokinetics of CsA and two main primary metabolites, AM1 and AM4N, in patients with rheumatic/autoimmune diseases. METHODS: Thirty-eight subjects, average age (years± SD) 46.8 (±11.6) years with rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, ankylosing spondylitis and undifferentiated SpA were included in an observational open study. The single dose pharmacokinetics (area under the concentration-time curve of CsA and its metabolites (AUC) and other PK parameters) were determined over a 24 h period following oral administration of 1.3 mg/kg oral CsA. Two CsA formulations-Neoral and the Czech generic substitute Consupren®, were used. Pharmacokinetic analysis was performed on all 38 patients after administration of a single dose of CsA (1.34 mg/ kg/day). In 12 patients only, a second series of blood samples was taken to calculate monitored PK parameters under steady state conditions. RESULTS: Pharmacokinetic assessment showed AUC(0-24) 3009.66 ± 1449.78 ng/ml.h and C(max) 827.84 ± 425.84 after administration of a single dose of CSA, AUC(0-24) 3698.50 ± 2147 ng/ml.h and C(max) 741 ± 493 ng/ml after repeated dose. The proportion of the AM1 metabolite (AUC(0-24)) after a single dose of CsA corresponded to 40% of the parent compound and to approximately 35% of the parent compound in steady state conditions. The proportion of AM4N metabolite was low in both conditions and represented only 3 and 4.5% after a single dose and at steady state, respectively. CONCLUSION: The pharmacokinetic data (AUC(CsA), C(max)) for the whole 24 h interval were similar to the published findings, mainly under steady state conditions. The AM1 (AUC(0-24)) after a single dose of CsA and in steady state conditions represented about 40% of the parent drug. The ratio of AM4N metabolite was low in both conditions.
22800698 [Preliminary study of the relationship between tumor like Sjögren's syndrome and malignan 2012 Apr OBJECTIVE: To investigate the clinical and laboratory characteristics of tumor like Sjögren's syndrome (TLSS) patients and non-tumor like Sjögren's syndrome (NTLSS) and the incidence of lymphoma in patients of Sjögren's syndrome (SS). METHODS: A retrospective analysis was carried out in 199 primary SS (including TLSS) patients who were recruited in Peking University School and Hospital of Stomatology from 1998 to 2010. Clinical and laboratory information were collected. The patients were divided into two groups: TLSS (n = 25) and NTLSS (n = 174). Clinical and laboratory characteristics were compared between these two groups by a statistical analysis. RESULTS: Of the 25 TLSS patients, 23 had enlargements of parotid glands and 2 had enlargements of submandibular glands. There were significant differences of salivary scintigraphy appearance (P = 0.018), hypergammaglobulinemia (P = 0.014), rheumatoid factor positive rate (P = 0.001), formation of the ectopic germinal centers (P = 0.014), double positive rate of anti-SSA antibody and anti-SSB antibody (P < 0.001) between the TLSS and NTLSS patients. Among the 25 TLSS patients, 3 developed lymphomas, accounting for 1.5% (3/199) of the total 199 patients and 12% (3/25) of the TLSS patients. Lymphoma subtypes included one diffused large B-cell lymphoma and two mucosa-associated lymphoid tissue lymphoma. There was no lymphoma detected in NTLSS patients. CONCLUSIONS: There are clinical and laboratory differences between TLSS and NTLSS patients, with a more tendency to develop lymphomas in TLSS patients.
21078710 A randomized controlled trial of the cost-effectiveness of ultrasound-guided intraarticula 2011 Feb OBJECTIVE: We studied whether sonographic needle guidance affected the outcomes of intraarticular (IA) injection for inflammatory arthritis. METHODS: Joints with inflammatory arthritis (n = 244; 76% rheumatoid arthritis, 3% small joints, 51% intermediate, and 46% large) were randomized to injection by conventional palpation-guided anatomic injection (120 joints) or sonographic image-guided injection enhanced with a 1-handed reciprocating procedure device mechanical syringe (124 joints). A 1-needle, 2-syringe technique was used. After IA placement and synovial space dilation were confirmed by sonography, a syringe exchange was performed, and triamcinolone acetonide was injected with the second syringe through the indwelling IA needle. Baseline pain, procedural pain, pain at outcome (2 weeks and 6 months), responders, therapeutic duration, reinjection rates, total cost, and cost per responder were determined. RESULTS: Relative to conventional palpation-guided methods, sonographic guidance for injection of inflammatory arthritis resulted in an 81% reduction in injection pain (p < 0.001), 35% reduction in pain scores at outcome (p < 0.02), 38% increase in the responder rate (p < 0.003), 34% reduction in the non-responder rate (p < 0.003), 32% increase in therapeutic duration (p = 0.01), 8% reduction ($7) in cost/patient/year, and a 33% ($64) reduction in cost/responder/year for a hospital outpatient (p < 0.001). CONCLUSION: Sonographic needle guidance improves the performance, clinical outcomes, and cost-effectiveness of IA injections for inflammatory arthritis. (Clinical Trial Identifier NCT00651625).
21794796 [Sjögren's syndrome and pancreatic affection]. 2011 Mar Sjögren's syndrome (SS) is an autoimmune disorder affecting primarily the exocrine glands, leading to keratoconjunctivitis sicca (KCS) and xerostomia, but that can also include extraglandular features(1). Due the anatomical, physiological and pathological similarity between the pancreas and the salivary glands, it has been described that the pancreas it is not exempt from the damage produced by this syndrome. Some authors have assessed pancreatic involvement of SS by analyzing the histopathological changes, evaluating the pancreatic endocrine and exocrine function (serum pancreatic enzymes, elastase, lipase or trypsin determinations, N-benzoyl-L-tyrosyl-para-aminobenzoic acid excretion test, etc), searching specific pancreatic antibodies (antiductal) or performing endoscopic retrograde colangiopancreatography or noninvasive imaging studies such as computed tomography or ultrasound. Herein we review the literature regarding the prevalence and type of pancreatic involvement in the SS and we discuss the differential diagnosis with multiorganic Lymphoproliferative Syndrome.
22568276 Primary Sjögren's syndrome or multiple sclerosis? Our experience concerning the dilemma o 2011 The authors present the case of a 50 years old woman who during 3 years had a transient right limbs palsy, and numerous episodes of unilateral/bilateral optic neuropathy. The CSF and MRI examinations did not sustain the diagnosis of multiple sclerosis (MS). After 2 years from the onset, she presented bilateral trigeminal neuropathy, and after 9 months the anti-SS-A and anti SS-B antibodies were positive. The sialography and the minor salivary ducts biopsy (in the absence of xerostomia and xerophthalmia) have established the diagnosis of primary Sjögren's syndrome (pSS). Subsequently, the patient presented spastic paraparesis, the clinical and imagistical features have suggested the diagnosis of acute transverse myelitis C4-T4. The treatment administered (corticosteroids and IGIV) improved the clinical state. The authors analyse then cases with SLE and cases with pSS, whose initial diagnosis was MS possibly with no evidence of collagen tissue disorders (CD) for many years. In conclusion, screening for biomarkers of SLE or pSS should be systematically performed in a case of acute or chronic myelopathy. Some laboratory tests as CSF examination, the antibodies type, cranial and spinal MRI, are useful for the differential diagnosis with MS. In a neurological clinically isolated syndrome (CIS) the diagnosis of MS should be precautiously established; the close follow-up of patients is always necessary, those with atypical neurological symptoms for MS, relapsing-remitting form, or lack of response to the common treatment for MS, should be examined for CD.
21401925 Comparative efficacy of a secretory phospholipase A2 inhibitor with conventional anti-infl 2011 Mar 14 INTRODUCTION: Previously, secretory phospholipase A2 (sPLA2) inhibition has been used as an adjunct to conventional rheumatoid arthritis therapy in human clinical trials without significant improvement of arthritic pathology. In this study, we compared the efficacy of a potent and orally active group IIa secretory phospholipase A2 inhibitor (sPLA2I) to conventional anti-arthritic agents; infliximab, leflunomide and prednisolone, in a rat model of antigen-induced arthritis. METHODS: Initially, to establish efficacy and dose-response, rats were orally dosed with the sPLA2I (1 and 5 mg/kg) two days prior to arthritis induction, and then daily throughout the 14-day study period. In the second trial, rats were orally dosed with the sPLA2I (5 and 10 mg/kg/day) beginning two days after the induction of arthritis, at the peak of joint swelling. Separate groups of rats were also dosed with the tumour necrosis factor-alpha (TNF-α) inhibitor infliximab (single 3 mg/kg i.v. injection), leflunomide (10 mg/kg/day, oral) or prednisolone (1 mg/kg/day, oral) at this same time point and used as comparative treatments. RESULTS: In the pathology prevention trial, both 1 and 5 mg/kg dose groups of sPLA2I demonstrated a significant reduction in joint swelling and gait disturbances; however, only the higher 5 mg/kg dose resulted in significantly reduced histopathology scores. In the post-induction trial, rats dosed with sPLA2I showed a significant improvement in joint swelling and gait scoring, whereas none of the conventional therapeutics achieved a significant decrease in both of these two disease markers. Histopathological scoring at the end-point of the study demonstrated significantly reduced median scores in rats treated with 10 mg/kg sPLA2I and leflunomide. CONCLUSIONS: The results from this study suggest a pathogenic role for sPLA2 enzymes in this model of arthritis in rats, and the potential clinical utility of sPLA2 inhibition as a safer, and more effective, alternative to conventional anti-arthritic therapeutics.
20936538 Attenuation of arthritis in rodents by a novel orally-available inhibitor of sphingosine k 2011 Apr Pro-inflammatory cytokines like TNF-α activate sphingosine kinase (SK). Therefore, inhibition of SK is a potential molecular target for the treatment of rheumatoid arthritis. AIMS: The primary goal of this study was to assess the efficacy of ABC249640 (a selective SK-2 inhibitor) in two models of rodent arthritis. A secondary goal was to evaluate the pharmacological profile of ABC294640, when given in combination with methotrexate. METHODS: The efficacy of ABC294640 was determined by paw diameter/volume measurements, histological evaluations, and micro-CT analyses. RESULTS: ABC294640 attenuated both collagen-induced arthritis in mice, as well as adjuvant-induced arthritis in rats. With the adjuvant arthritis model, the prophylactic efficacy profile of ABC294640 was similar to indomethacin. Of note, ABC294640 reduced the bone and cartilage degradation, associated with adjuvant-induced arthritis. Rats treated with a suboptimal dose of MTX (50 μg/kg/day) in combination with ABC249640 (100 mg/kg/day) had better anti-arthritis effects in the adjuvant model, than treatment with either agent alone. CONCLUSION: Our results suggest that ABC249640 is an orally available drug candidate with a good pre-clinical efficacy profile for the prevention and/or treatment of RA.
21724708 Plectranthus amboinicus attenuates inflammatory bone erosion in mice with collagen-induced 2011 Sep OBJECTIVE: Plectranthus amboinicus has been known to treat inflammatory diseases or swelling symptoms. We investigated whether P. amboinicus exhibited an inhibitory effect on osteoclastogenesis in vitro and inflammatory bone erosion in collagen-induced arthritis (CIA) mice, an animal model of rheumatoid arthritis. We attempted to identify the active component of P. amboinicus involved in regulation of osteoclastogenesis. METHODS: We treated M-CSF- and RANKL-stimulated murine bone marrow-derived macrophages (BMM) and RANKL-induced RAW264.7 cells with different concentrations of P. amboinicus or rosmarinic acid, a phytopolyphenol purified from P. amboinicus, to monitor osteoclast formation by TRAP staining. The mechanism of the inhibition was studied by biochemical analysis such as RT-PCR and immunoblotting. CIA mice were administered gavages of P. amboinicus (375 mg/kg) or placebo. Then clinical, histological, and biochemical measures were assessed to determine the effects of P. amboinicus on synovial inflammation and bone erosion by H&E staining of the inflamed joints and ELISA. RESULTS: Rosmarinic acid strongly inhibited RANKL-induced NF-κB activation and nuclear factor of activated T cells c1 (NFATc1) nuclear translocation in BMM, and also inhibited RANKL-induced formation of TRAP-positive multinucleated cells. A pit formation assay and the CIA animal model showed that P. amboinicus significantly inhibited the bone-resorbing activity of mature osteoclasts. CONCLUSION: We postulated that rosmarinic acid conferred the inhibitory activity on P. amboinicus for inhibition of osteoclastogenesis via downregulation of RANKL-induced NFATc1 expression. Our results indicated the possibility of P. amboinicus as a new remedy against inflammatory bone destruction.
23055580 Thesis, antithesis, and synthesis in periodontal and systemic interlink. 2012 Apr The theory of focal infection, which was promulgated during the 19(th) and early 20(th) centuries, stated that "foci" of sepsis were responsible for the initiation and progression of a variety of inflammatory diseases such as arthritis, peptic ulcers, and appendicitis. In the oral cavity, therapeutic edentulation was common as a result of the popularity of the focal infection theory. Since many teeth were extracted without evidence of infection, thereby providing no relief of symptoms, the theory was discredited and largely ignored for many years. Recent progress in classification and identification of oral microorganisms and the realization that certain microorganisms are normally found only in the oral cavity have opened the way for a more realistic assessment of the importance of oral focal infection. It has become increasingly clear that the oral cavity can act as the site of origin for dissemination of pathogenic organisms to distant body sites, especially in immunocompromised hosts such as patients suffering from malignancies, diabetes, rheumatoid arthritis, or in patients undergoing other immunosuppressive treatment. A number of epidemiological studies have suggested that oral infection, especially periodontitis, may be a risk factor for systemic diseases.
22505941 TNF-Alpha in the Locomotor System beyond Joints: High Degree of Involvement in Myositis in 2012 The importance of TNF-alpha in arthritis is well documented. It may be that TNF-alpha is also markedly involved in muscle inflammation (myositis). An animal model where this can be investigated is needed. A newly developed rabbit myositis model involving pronounced muscle overuse and local injections of substances having proinflammatory effects was therefore used in the present study. The aim was to investigate the patterns of TNF-alpha expression in the developing myositis and to evaluate the usefulness of this myositis model for further TNF-alpha research. Human rheumatoid arthritis (RA) synovial tissue was examined as a reference. TNF-alpha immunoexpression and TNF-alpha mRNA, visualized via in situ hybridization, were detected in cells in the inflammatory infiltrates of the affected muscle (soleus muscle). Coexistence of TNF-alpha and CD68 immunoreactions was noted, suggesting that the TNF-alpha reactive cells are macrophages. Expression of TNF-alpha mRNA was also noted in muscle fibers and blood vessel walls in areas with inflammation. These findings demonstrate that TNF-alpha is highly involved in the myositis process. The model can be used in further studies evaluating the importance of TNF-alpha in developing myositis.
22378270 Inflammatory bone loss: pathogenesis and therapeutic intervention. 2012 Mar 1 Bone is a tissue undergoing continuous building and degradation. This remodelling is a tightly regulated process that can be disturbed by many factors, particularly hormonal changes. Chronic inflammation can also perturb bone metabolism and promote increased bone loss. Inflammatory diseases can arise all over the body, including in the musculoskeletal system (for example, rheumatoid arthritis), the intestine (for example, inflammatory bowel disease), the oral cavity (for example, periodontitis) and the lung (for example, cystic fibrosis). Wherever inflammatory diseases occur, systemic effects on bone will ensue, as well as increased fracture risk. Here, we discuss the cellular and signalling pathways underlying, and strategies for therapeutically interfering with, the inflammatory loss of bone.
23547396 [Macrophage activation syndrome: report on three cases]. 2012 The macrophage activation syndrome (MAS) is a rare and potentially fatal disease. This syndrome is founded on congenital or acquired dysfunction of NK cells resulting in secondary activation and proliferation of macrophages with excessive cytokine production and organ infiltration. Causes of acquired MAS include viral infections (chiefly EBV and CMV), malignancies, and autoimmune diseases. The macrophage activation syndrome is usually associated with juvenile idiopathic arthritis and adult-onset Still's disease and rarely with rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, and systemic sclerosis. Fever, hepatosplenomegaly, lymphadenopathy, and bi- or pancytopenia in peripheral blood represent typical symptoms of MAS. Hyperferritinemia, hypertriglyceridemia, hypertransaminasemia, and hypofibrinogenemia are among the common laboratory findings. The macrophage activation syndrome is a life-threatening condition requiring aggressive therapy due to multiple organ dysfunction. Treatment also includes elimination of the triggering infection and high-dose glucocorticosteroids. Second-line therapy is based on cyclosporin, intravenous immunoglobulins, and etoposide. The present work focuses on diagnostic and therapeutic difficulties in three patients with the macrophage activation syndrome.
21833532 Modulation of immune and inflammatory responses on experimental arthritis following intraa 2012 Sep In spite of popularity of TNF-α antagonist in the treatment of rheumatoid arthritis (RA), their modes of action are not fully understood. In the present study, we further explore the effects of gene transfer route of a TNF-α antagonist on arthritis. Recombinant adeno-associated virus 2 (rAAV2) encoding rat TNF receptor-immunoglobulin Fc (ratTNFR:Fc) fusion gene was injected intraarticularly in rats with collagen-induced arthritis (CIA). As revealed by examination of the clinical, radiographical, and histological aspects, local gene transfer of rAAV2/ratTNFR:Fc ameliorated the arthritis symptoms and inhibited the development of CIA. Compared with the vector control group, expressions of TNF-α, IL-1, and IFN-γ were down-regulated, and IL-10 release was up-regulated in the rAAV2/ratTNFR:Fc-treated group. Furthermore, administration of rAAV2/ratTNFR:Fc ameliorated the enlargement of spleen and significantly reduced spleen cell proliferation. Low level of nitric oxide (NO) in spleen was observed in CIA rats following the delivery of rAAV2/ratTNFR:Fc when compared to the vector control group. This study provides the evidence that intraarticular delivery of rAAV2/ratTNFR:Fc suppress the progression of arthritis by restoring the balance between pro-inflammatory and anti-inflammatory cytokines and inhibiting spleen cell proliferation. Our findings also implicate that the down-regulation of NO release on arthritis is involved in the anti-inflammatory mechanisms of TNF-α antagonist.
21384333 Local expression of interleukin-27 ameliorates collagen-induced arthritis. 2011 Aug OBJECTIVE: To determine the mechanism of action of interleukin-27 (IL-27) against rheumatoid arthritis (RA). METHODS: Adenovirus containing IL-27 transcript was constructed and was locally delivered into the ankles of mice with collagen-induced arthritis (CIA). Progression of arthritis was determined in treated and untreated mice by measuring ankle circumference and through histologic analysis. IL-17 and its downstream targets as well as cytokines promoting Th17 cell differentiation were quantified by enzyme-linked immunosorbent assay in CIA mouse ankles locally expressing adenoviral IL-27 as well as in control-treated mouse ankles. Ankles from both treatment groups were immunostained for neutrophil and monocyte migration (macrophages in the tissue). Finally, vascularization was quantified by histology and by determining ankle hemoglobin levels. RESULTS: Ectopic expression of IL-27 in CIA mice ameliorated inflammation, lining hypertrophy, and bone erosion as compared with control-treated CIA mice. Serum and joint levels of IL-17 were significantly reduced in the IL-27-treated group compared with the control-treated group. Two of the main cytokines that induce Th17 cell differentiation and IL-17 downstream target molecules were greatly down-regulated in CIA mouse ankles receiving forced expression of IL-27. The control mice had higher levels of vascularization and monocyte trafficking than did mice ectopically expressing IL-27. CONCLUSION: Our results suggest that increased levels of IL-27 relieve arthritis in CIA mouse ankles. This amelioration of arthritis involves a reduction in CIA mouse serum and joint levels of IL-17 and results in decreased IL-17-mediated monocyte recruitment and angiogenesis. Hence, the use of IL-27 may be a strategy for treatment of patients with RA.
23252659 Behçet disease-associated uveitis successfully treated with golimumab. 2013 Apr Over the past decade, the off-label use of biologic agents such as TNF-α antagonists, including infliximab and adalimumab, has improved the treatment armamentarium for refractory immune-mediated uveitis, with particular success in Behçet disease-associated uveitis. Golimumab is a novel fully human anti-TNF-α monoclonal antibody that has been approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, with very promising results. Herein, the authors present the use of GLM in a case of Behçet uveitis refractory to other TNF-α blockers. There are only two reports in the literature about the use of GLM in uveitis, describing four patients with JIA-associated uveitis and a case of idiopathic retinal vasculitis. To the authors' knowledge, this is the first report about the use of GLM in Behçet uveitis.
22720456 Targeting CVD risk in chronic connective tissue disease. 2012 Jan Chronic inflammatory rheumatological conditions are associated with an increased burden of cardiovascular disease (CVD). In both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) most excess mortality is cardiovascular. Increased CVD risk is also associated with psoriatic arthritis, ankylosing spondylitis, antiphospholipid syndrome and systemic sclerosis. Several studies report that CVD mortality increases early in disease in RA, with increased risk of MI within one year and increased risk of hospital admission for CVD within seven years of diagnosis. A linear association has been demonstrated between subclinical carotid atherosclerosis and raised inflammatory markers. SLE is associated with 2-10 times the risk of a CVD event compared with the general population. CVD is now a leading cause of morbidity and mortality in SLE. Antiphospholipid antibodies are associated with accelerated atherosclerosis, as well as thromboses. Atherogenesis in the context of autoimmune disease results from a complex interplay between traditional risk factors, disease-specific factors and drug-related adverse effects. Chronic inflammation itself modifies the lipid profile.