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21419078 [Systematic review and meta-analysis of randomized controlled trials of Chinese herbal med 2011 Mar BACKGROUND: Chinese herbal medicine (CHM) has been widely used in the treatment of Sjogren's syndrome. However, there remains no systematic review to assess the effectiveness and safety of CHM. OBJECTIVE: To assess the effectiveness and safety of CHM in the treatment of Sjogren's syndrome. SEARCH STRATEGY: Literature was searched from PubMed, the Cochrane Library (Issue 3, 2010), the China National Knowledge Infrastructure Database, the Chongqing VIP Chinese Science and Technology Periodical Database, the Chinese Biomedical Literature Database (SinoMed), Wanfang Data and the Traditional Chinese Medical Periodical Literature Database. The time limitation ran from the commencement of each database to October 15, 2010. INCLUSION CRITERIA: Randomized controlled trials (RCTs) testing CHM alone or in combination with Western medicine (WM) against WM or placebo used alone were included. DATA EXTRACTION AND ANALYSIS: Two authors collected data independently. The assessment of methodological quality was based on the Cochrane handbook and the data were analyzed by using RevMan 5.0.17 software. Heterogeneity of the included studies was tested and use of statistical model was based on the heterogeneity. The efficacy measure was relative risk (RR) or mean difference with a 95% confidence interval (CI). RESULTS: A total of 52 RCTs involving 3 886 patients were included. The included trials were all of low quality. CHM was superior in improving clinical symptoms to WM, with statistical significance between the groups (RR:1.36; 95% CI: 1.24-1.49); CHM plus WM was better than WM used alone (RR: 1.38; 95% CI:1.30-1.46). CHM improved lacrimal gland function more effectively than WM, with statistical significance between the groups (RR:2.12; 95% CI:1.06-3.18); CHM plus WM was better than WM used alone (RR:1.90; 95% CI: 0.99-2.81). CHM was superior to WM in the improvement of erythrocyte sedimentation rate (RR:-9.63; 95% CI:-15.73--3.52), and CHM plus WM was also more effective than WM used alone (RR:-8.42; 95% CI:-14.71--2.13). However, there was no statistical difference between groups in other immune index (C-reactive protein, rheumatoid factor, IgG, IgA and IgM). The reported adverse effects of CHM were mainly gastrointestinal symptoms, such as diarrhea. The incidence of adverse effects of WM was higher than that of CHM. CONCLUSION: CHM appears to improve the symptoms of Sjogren's syndrome. However, due to the low quality of included studies, further well-designed multicenter and large-scale RCTs are still needed to evaluate the beneficial effects of CHM.
20943291 [Small fibre neuropathy in primary Sjögren syndrome]. 2011 Mar PURPOSE: About forty percent of the patients with primary Sjögren's syndrome (pSS) experience chronic neuropathic pain with normal electrodiagnostic studies. Two previous studies suggest that chronic neuropathic pain in pSS is due to small fiber neuropathy (SFN). Quantification of epidermal nerve fiber density after skin biopsy has been validated to diagnose small fiber neuropathy. METHODS: Skin biopsy was performed in 14 consecutive pSS patients (satisfying the american-european classification criteria) with chronic neuropathic pain and normal electrodiagnostic studies suggesting SFN. RESULTS: Fourteen female pSS patients exhibited chronic neuropathic pain [burning sensation (n=14), prickling (n=4), dysesthesia (n=8)] with paroxystic exacerbations (n=10) and allodynia (n=13), for a mean period of 18.4±12.4 months. Neuropathic pain involved mostly hands and feet (n=13), with a distal (n=9) and leg (n=4) predominant distribution. Neurological examination disclosed normal deep tendon responses and absence of motor weakness (n=14). Small fiber neuropathy was confirmed by skin biopsy in 13 cases. Epidermal nerve fiber density was decreased in distal [(n=12), mean 3.5±1.7 fibers/mm (N>6.9)] and proximal site of biopsy [(n=9), mean 7.04±2.63 fibers/mm (N>9.3)]. CONCLUSION: Small fiber neuropathy is commonly responsible of chronic neuropathic pain in pSS. Prevalence, physiopathology and neurological evolution of such neuropathies still remain unknown.
23405545 Sjogren's syndrome presenting with hypokalemic periodic paralysis. 2012 Jul We report a rare case of a 38-year-old female who presented with sudden onset flaccid quadriplegia and respiratory arrest with no significant past clinical history. She was later found to have hypokalemia due to distal renal tubular acidosis and further diagnosed as case of Sjogrens Syndrome.
23052840 A potential role of the GRO-α/CXCR2 system in Sjögren's syndrome: regulatory effects of 2013 Feb Chemokines, small pro-inflammatory cytokines, are involved in migration of inflammatory cells in inflamed tissues and recent studies established their role in angiogenesis, hematopoiesis, cancer and autoimmune conditions. Growth related oncogene-alpha (GRO-α), a member of the CXC chemokine family, and its receptor CXCR2 are involved in the inflammatory processes. Since there is no previous report that supports a possible role of GRO-α/CXCR2 receptor complex during inflammation and neovascularization existing in the autoimmune disease Sjögren's syndrome (SS), in this study, we examined CXCR2 and its ligand GRO-α expression in SS tissues. Immunohistochemistry revealed that GRO-α and its receptor CXCR2 were expressed at high levels in diseased tissues compared to healthy controls. In addition, human salivary gland epithelial cells (SGEC) cultures were submitted to a pro-inflammatory microenvironment using cytokines IL-6 and TNF-α in order to demonstrate that CXCR2 may change its initial expression pattern to another under inflammatory condition. The data show an increased expression of CXCR2 depending on the inflammatory cytokine used in culture in a time-dependent manner. Furthermore, silencing of the pro-angiogenic chemokine GRO-α is proportionally correlated with decreased expression of CXCR2 in pro-inflammatory cytokine-stimulated SGEC indicating the GRO-α/CXCR2 complex as a novel therapeutic target for the chronic inflammatory disease Sjögren's syndrome.
23185418 Improved flow cytometric assessment reveals distinct microvesicle (cell-derived microparti 2012 INTRODUCTION: Microvesicles (MVs), earlier referred to as microparticles, represent a major type of extracellular vesicles currently considered as novel biomarkers in various clinical settings such as autoimmune disorders. However, the analysis of MVs in body fluids has not been fully standardized yet, and there are numerous pitfalls that hinder the correct assessment of these structures. METHODS: In this study, we analyzed synovial fluid (SF) samples of patients with osteoarthritis (OA), rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). To assess factors that may confound MV detection in joint diseases, we used electron microscopy (EM), Nanoparticle Tracking Analysis (NTA) and mass spectrometry (MS). For flow cytometry, a method commonly used for phenotyping and enumeration of MVs, we combined recent advances in the field, and used a novel approach of differential detergent lysis for the exclusion of MV-mimicking non-vesicular signals. RESULTS: EM and NTA showed that substantial amounts of particles other than MVs were present in SF samples. Beyond known MV-associated proteins, MS analysis also revealed abundant plasma- and immune complex-related proteins in MV preparations. Applying improved flow cytometric analysis, we demonstrate for the first time that CD3(+) and CD8(+) T-cell derived SF MVs are highly elevated in patients with RA compared to OA patients (p=0.027 and p=0.009, respectively, after Bonferroni corrections). In JIA, we identified reduced numbers of B cell-derived MVs (p=0.009, after Bonferroni correction). CONCLUSIONS: Our results suggest that improved flow cytometric assessment of MVs facilitates the detection of previously unrecognized disease-associated vesicular signatures.
21763790 Anti-CD 20 monoclonal antibody (rituximab) treatment for inflammatory ocular diseases. 2011 Nov Rituximab is a monoclonal antibody directed against the CD20 antigen expressed on B cells and widely used in the treatment of non-Hodgkin's lymphoma and rheumatoid arthritis. There is a growing amount of literature which suggests that rituximab may be useful for inflammatory ocular diseases and intraocular lymphoma. Few cases have been reported on treatment of refractory scleritis, peripherative ulcerative keratitis, uveitis and ocular surface inflammatory disorders. Rituximab may be effective in the treatment of ocular inflammatory diseases in particular the most aggressive, recalcitrant and sight-threatening forms of inflammation such as uveitis associated to juvenile idiopathic arthritis. We review the literature covering the use of Rituximab in these conditions and report our results on the efficacy of Rituximab in the treatment of 8 children with very severe and long-standing uveitis who failed to respond to one or more TNF blockers. Our patients showed improvement in activity of uveitis, reduction of concomitant corticosteroids and immunosuppressants after a mean follow-up time of 14.87 months on rituximab. No serious adverse events were encountered in our treated patients. Although further studies are needed for assessing the efficacy of rituximab and the exact dosing regimen, rituximab may be considered as a treatment alternative in patients with the most aggressive forms of inflammatory ocular diseases who fail to respond to conventional and anti-TNF immunosuppressive agents.
23037479 Angioedema of the periorbital region that developed during treatment with etanercept in a 2012 A 78-year-old Japanese man with adult-onset Still's disease that was refractory to conventional treatment, such as prednisolone (PSL) concomitant with methotrexate (MTX). Etanercept (50 mg/week) was added to PSL (12.5 mg/day) and MTX (12 mg/week). His manifestation improved dramatically, nonetheless massive edema of the periorbital region developed by the fourth injection, which kept his palpebral fissure completely closed. There was also a marked injection site reaction to etanercept. A diagnosis of angioedema due to etanercept was thus made, and the drug was discontinued. His angioedema began to ameliorate soon after antihistamines were introduced without any critical involvement, such as laryngeal obstruction.
22835660 Low levels of vitamin-D are associated with neuropathy and lymphoma among patients with Sj 2012 Sep BACKGROUND/PURPOSE: Primary Sjögren's syndrome (SS) is a chronic autoimmune disease primarily involving the exocrine glands. The clinical picture of SS ranges from exocrinopathy to systemic disease affecting the lung, kidney, liver, skin, musculockeletal and nervous systems. The morbidity of SS is mainly determined by extraglandular disease and increased prevalence of lymphoma. Environmental and hormonal factors, such as vitamin-D may play a role in the pathogenic process and disease expression. Thus, we aimed to evaluate levels of vitamin-D and their association with manifestations of SS. METHODS: Vitamin-D levels were determined in 176 primary SS patients and 163 matched healthy volunteers utilizing the LIAISON chemiluminescent immunoassays (DiaSorin-Italy). A correlation between vitamin-D levels and clinical and serological manifestations of SS was performed. RESULTS: Mean vitamin-D levels were comparable between SS patients and control 21.2 ± 9.4 ng/ml and 22.4 ± 10 ng/ml, respectively. Peripheral neuropathy was diagnosed in 23% of SS patients and associated with lower vitamin-D levels (18.6 ± 5.5 ng/ml vs. 22.6±8 ng/ml (p = 0.04)). Lymphoma was diagnosed in 4.3% of SS patients, who had lower levels of vitamin-D (13.2 ± 6.25 ng/ml), compared to SS patients without lymphoma (22 ± 8 ng/ml), (p = 0.03). Other clinical and serological manifestations did not correlate with vitamin-D status. CONCLUSIONS: In this study, low levels of vitamin-D correlated with the presence of peripheral neuropathy and lymphoma among SS patients. The link between vitamin-D and neuropathy or lymphoma was reported in other conditions, and may support a role for vitamin-D in the pathogenesis of these processes. Plausible beneficial effect for vitamin-D supplementation may thus be suggested.
22079910 Management of severe rheumatological disease in the burn center. 2012 May In recent years, Burn Center has evolved to become a "wound intensive care unit" treating disease processes other than those due to thermal injury. Recent data have shown that more than 16% of admissions to Burn Centers are for nonburn injuries, particularly severe dermatologic diseases. The role of the Burn Center has been expanded to include treatment of patients with severe cutaneous manifestations of rheumatologic diseases. This approach has not been described before. All collagen vascular disease admissions to the Burn Center from 2005 to 2010 have been reviewed. There were 16 admissions where intensive wound management was a major component of the disease management. Disease processes included systemic lupus erythematosus, progressive systemic sclerosis, Raynaud's phenomenon, antiphospholipid syndrome, and dermatomyositis, among others. The authors describe five of these cases in detail. Comanagement of these patients by the Rheumatology and Burn services led to outstanding, successful outcomes. Collagen vascular diseases represent another area where the Burn Center may be the appropriate site for therapy.
21924496 Contribution of IL-13 to early exocrinopathy in Id3-/- mice. 2011 Oct Id3-/- mice represent a model for T cell mediated primary Sjogren's syndrome (PSS). An intriguing feature of this disease model is the early appearance of impaired salivary function or exocrinopathy prior to lymphocytic infiltration of the salivary glands. This phenomenon prompted us to examine the role of cytokines produced by T cells in the systemic regulation of gland function. A comprehensive examination of serum cytokine profiles revealed elevated levels of IL-13 in Id3-/- mice. We found that the increase in serum IL-13 levels in Id3-/- mice was largely dependent on αβ T cells. Removal of αβ T cells in Id3-/- mice also eliminates disease symptoms, including lymphocytic infiltration in the gland tissues, and impaired saliva production. We further show that the number of mast cells in the salivary glands of Id3-/- mice is significantly increased, in a trend inversely related to the saliva production. This increase in the number of mast cells is also dependent on the presence of αβ T cells. Treatment of young Id3-/- mice with anti-IL-13 antibodies over a two-month period resulted in a reduction of both serum IL-13 levels and the number of mast cells in the salivary gland tissues, as well as correspondingly improved saliva production. These findings indicate a potentially important role for IL-13 in gland regulation and disease pathology.
21786120 Primary Sjögren's syndrome in Moroccan patients: characteristics, fatigue and quality of 2012 Sep Our aim was to evaluate fatigue and quality of life (QoL) in Moroccan patients with primary Sjögren's syndrome (PSS) and determine their correlates with disease-related parameters. Fifty-seven consecutive patients with PSS according to the American-European Consensus group (AEGG) criteria were included. Demographic, clinical, biological and immunological characteristics for all patients were collected. Xerostomia was demonstrated by histological grading of lower lip glandular biopsy. A Schirmer test was performed to measure lachrymal flow. Oral, ocular, skin, vaginal and tracheal dryness were evaluated by using a visual analogue scale (VAS). Fatigue was assessed by the Multidimensional assessment of fatigue (MAF) and the QoL by using the generic instrument: SF-36. 90% of our patients were women. The mean age of patients was 53.73 ± 7.69 years, and the mean disease duration was 5.38 ± 4.11 years. The mean oral dryness was 68.38 ± 20.29, and the mean ocular dryness was 51.91 ± 14.03. The mean total score of the MAF was 26.73 ± 8.33, and 87.5% of our patients experienced severe fatigue. Also, physical and mental domains of QoL were altered in a significant way, and the severity of fatigue had a negative impact on SF-36 scores. MAF and SF-36 scores were correlated with the delay of diagnosis, the intensity of xerostomia and the activity of joint involvement. A low socioeconomic and educational level had a negative impact on fatigue scores and QoL. Histological grading of lower lip glandular biopsy, immunological status and the severity of systemic involvement had no correlations with fatigue scores or the alteration of QoL. Patients receiving antidepressant have lesser fatigue and those receiving Methotrexate have better SF-36 scores. In our data, there was a high prevalence of fatigue in Moroccan patients with PSS associated with altered QoL. Severe fatigue and reduced QoL seem to be related to the severity of joint involvement, xerostomia and both educational and socioeconomic levels. Also, treatment with methotrexate and antidepressant seems to improve patients' living and QoL. An appropriate therapeutic intervention for depression and articular manifestations in PSS should be applied to improve patients' living.
21325391 Absence of up-regulation for a proliferation-inducing ligand in Sjögren's sialadenitis le 2011 Jul OBJECTIVE: To determine whether a proliferation-inducing ligand (APRIL) has a role in the survival of plasma cells infiltrating salivary glands from SS patients. METHODS: We performed immunological staining for APRIL in minor salivary glands from SS with a pair of antibodies specifically recognizing APRIL-producing cells and secreted APRIL. RESULTS: Despite high leucocyte infiltration, APRIL-producing cells, identified as neutrophils, were rare in SS salivary glands. Keratinocytes from the adjacent oral epithelium also produced APRIL, but we never detected significant levels of secreted APRIL in SS salivary glands. We obtained similar results with B-cell lymphomas associated with SS. In fact, there was no significant difference in APRIL production and the level of secreted APRIL in these pathological samples compared with normal corresponding tissues. CONCLUSION: The combined observation that APRIL production is not up-regulated in lesions from SS patients, and that secreted APRIL is not retained in these lesions, indicates that plasma cells frequently present in SS lesions may not rely on APRIL for survival, as they do in other rheumatic diseases.
23469599 [Analysis of the clinical efficacy of yiqi fumai injection combined hydroxychloroquine sul 2012 Dec OBJECTIVE: To observe the clinical efficacy of Yiqi Fumai Injection (YFI) combined hydroxychloroquine sulfate tablet in the treatment of Sjogren's syndrome patients. METHODS: Eighty patients were randomly assigned to three groups. Forty patients in Group A were treated with YFI alone, 2. 6 g YFI added in 250 mL normal saline for intravenous dripping, once daily. Twenty patients in Group B took hydroxychloroquine sulfate alone, 0. 2 g each time, twice daily. Twenty patients in Group C were treated with YFI and hydroxychloroquine sulfate tablet (with the same dose and dosage as Group A and B). Fifteen days was taken as one course of treatment. The scores for dry mouth and dry eyes, the efficacy on salivary flow rate, Schirmer test, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and IgG, and so on were compared among the three groups before and after treatment. RESULTS: There was no significant difference in the laboratory parameters and clinical symptoms among the three groups before treatment. After treatment obvious improvement of the scores for dry mouth, the salivary flow rate, Schirmer test, ESR, CRP, and IgG was shown in all the 3 groups (P<0.05). Besides, the optimal effect was shown in Group C. Its total effective rate was 85% (17/20), better than that of Group A [80% (32/40)] and Group B [75% (15/20)], with no statistical difference (chi2 = 0.736 and 0. 695, P>0.05). CONCLUSION: YFU combined hydroxychloroquine sulfate tablet showed better effects in treating Sjogren's syndrome patients than using Chinese medicine or Western medicine alone.
20888090 [Acquired Gitelman syndrome associated with Sjögren's syndrome and scleroderma]. 2011 Aug Tubulopathy can complicate autoimmune diseases. It is usually a distal tubular acidosis, but Fanconi syndrome or Bartter syndrome has been exceptionally reported. We report a case of acquired Gitelman syndrome in a 32-year-old male who also presented diffuse scleroderma autoimmune thyroiditis, and Sjögren's syndrome. Only three cases of Sjögren syndrome associated with Gitelman syndrome have been previously reported in literature. The absence of other cases in the family and absence of mutation SLC12A3 emphasise the relation between autoimmune disease and this tubulopathy.
22956380 Girdlestone procedure: when and why. 2012 Jul Girdlestone is one of the options for treating an infected hip arthroplasty (along with isolated antibiotics, debridement, and one or two-stage exchange). The choice must be based on a list of previous considerations. RESULTS OF GIRDLESTONE: Major differences among different series are reported in literature: from 13% to 83% of patients are satisfied with the result. Healing of infection is attained in 80% to 100% of patients, but figures are worse in special subsets (rheumatoid arthritis, enterococcal and methicillin-resistant infections, or when cement is retained). Pain is reported as severe in 16% to 33% of patients, moderate in 24% to 53% and mild in 76%, while only some authors refer to "satisfactory pain relief". Up to 45% of geriatric patients are unable to walk and only 29% walk independently. The literature reports Harris Hip scores from 25 to 64. INDICATIONS FOR GIRDLESTONE: Absolute indications: non-ambulatory patients because of other problems or diseases, and impossible reimplantation (2nd-stage surgery) (unacceptable anaesthetic or surgical risk, technical difficulties, patient rejection). RELATIVE INDICATIONS: Dementia (risk of dislocation vs. severely reduced walking ability), immunocompromise (up to what degree of immune impairment do we accept to take the risk?), intravenous drug abuse (how can you prove it?).
22715234 Primary Sjögren's disease and its complications presenting with progressive paralysis. 2011 Jan 12 A 24-year-old female presented with generalised weakness, lethargy and aches in legs. She was subsequently found to be markedly hypokalaemic and have a metabolic acidosis. A diagnosis of distal renal tubular acidosis (RTA) was made. In addition to this failure to alkalinise her urine, she was unable to concentrate it and so a diagnosis of nephrogenic diabetes insipidus was reached. Further questioning revealed previous investigation of a connective tissue disorder thought to be primary Sjögren's syndrome. RTA is a recognised but rare complication of Sjögren's syndrome. Urinary alkalinisation using potassium bicarbonate was instituted; the patient responded well to treatment and is having outpatient follow-up.
22931668 [Effects of tumor necrosis factor-α on immunoregulatory activities of mesenchymal stem ce 2012 Aug Mesenchymal stem cells (MSC) are characterized by their potent immuno-regulatory activity, however our previous data have shown that MSC have no therapeutic effects on collagen-induced arthritis (CIA). To further clarify the complexity, the effects of tumor necrosis factor-alpha (TNF-α) on the in vitro and in vivo immunoregulatory activity of MSC were investigated in this study, as TNF-α is recognized as the key factor in the development of rheumatoid arthritis. The nuclear translocation of the inflammation-associated factor NF-κB was observed after human umbilical cord MSC were treated with TNF-α and the cell proliferation status was assessed by MTT test. The inhibitory effects of MSC or TNF-α-treated MSC on the mixed lymphocyte reaction, in which Wistar rat spleen mononuclear cells were served as the responders and the splenocytes from SD rat spleens as the stimulators, were also determined by the MTT test. Further, the therapeutic potentials of MSC or TNF-α-treated MSC were observed in a Wistar rat CIA model. The results showed that NF-κB translocated into the nuclei promptly after TNF-α treatment, though TNF-α had little effect on the MSC proliferation. MSC, whether pre-stimulated by TNF-α or not and when different doses were tested, exhibited obviously inhibitory effects on the proliferation of the lymphocytes (P < 0.001 for all groups tested), while MSC-treated by TNF-α displayed more potent suppression especially when low-density were used. Unexpectedly, the infiltration of inflammatory cells into the involved knees was aggravated by cell treatment and the pathological scores were significantly higher than those of controls (P < 0.05). It is concluded that the TNF-α exhibits different effects on immune regulation activity of MSC, and its underlying mechanism needs to further investigate.
23251456 Activation of Invariant NKT cells with glycolipid ligand α-galactosylceramide ameliorates 2012 OBJECTIVE: Invariant natural killer T (iNKT) cells regulate collagen-induced arthritis (CIA) when activated by their potent glycolipid ligand, alpha-galactosylceramide (α-GalCer). Glucose-6-phosphate isomerase (GPI)-induced arthritis is a closer model of human rheumatoid arthritis based on its association with CD4+ T cells and cytokines such as TNF-α and IL-6 than CIA. Dominant T cell epitope peptide of GPI (GPI325-339) can induce arthritis similar to GPI-induced arthritis. In this study, we investigated the roles of activation of iNKT cells by α-GalCer in GPI peptide-induced arthritis. METHODS: Arthritis was induced in susceptible DBA1 mice with GPI peptide and its severity was assessed clinically. The arthritic mice were treated with either the vehicle (DMSO) or α-GalCer. iNKT cells were detected in draining lymph nodes (dLNs) by flow cytometry, while serum anti-GPI antibody levels were measured by enzyme-linked immunosorbent assay. To evaluate GPI peptide-specific cytokine production from CD4+ T cells, immunized mice were euthanized and dLN CD4+ cells were re-stimulated by GPI-peptide in the presence of antigen-presenting cells. RESULTS: α-GalCer induced iNKT cell expansion in dLNs and significantly decreased the severity of GPI peptide-induced arthritis. In α-GalCer-treated mice, anti-GPI antibody production (total IgG, IgG1, IgG2b) and IL-17, IFN-γ, IL-2, and TNF-α produced by GPI peptide-specific T cells were significantly suppressed at day 10. Moreover, GPI-reactive T cells from mice immunized with GPI and α-GalCer did not generate any cytokines even when these cells were co-cultured with APC from mice immunized with GPI alone. In vitro depletion of iNKT cells did not alter the suppressive effect of α-GalCer on CD4+ T cells. CONCLUSION: α-GalCer significantly suppressed GPI peptide-induced arthritis through the suppression of GPI-specific CD4+ T cells.
21618207 Increased expression of interleukin-22 by synovial Th17 cells during late stages of murine 2011 Oct OBJECTIVE: Interleukin-22 (IL-22) is a mediator in antimicrobial responses and inflammatory autoimmune diseases. Although IL-22 and its receptor, IL-22R, have been identified in the synovium of rheumatoid arthritis patients, the source of IL-22 and its contribution to disease pathogenicity remain to be established. This study was undertaken to investigate the regulation of IL-22 by Th17 cells in vitro and to evaluate the potential for IL-22 depletion in an experimental arthritis model using mice deficient in the IL-1 receptor antagonist (IL-1Ra-/-). METHODS: Naive murine T cells were cultured under conditions leading to polarization of the cells into subsets of Th1, Th2, induced Treg, and Th17. Cytokines were measured in the culture supernatants, and the cells were analyzed by fluorescence-activated cell sorting. Tissue samples from the inflamed ankle synovium of IL-1Ra-/- mice were isolated, and messenger RNA levels of marker genes were quantified. IL-1Ra-/- mice were treated with neutralizing anti-IL-22 antibodies. Synovial cells were isolated from the inflamed tissue and sorted into fractions for analysis of cytokine production. RESULTS: In vitro tests showed that Th17 cells produced high levels of IL-22 after stimulation with IL-1 or IL-23. Interestingly, a synergistic increase in the production of IL-22 was observed after combining IL-1 and IL-23. In vivo, IL-1Ra-/- mice displayed a progressive erosive arthritis, characterized by up-regulation of IL-17 in mildly and severely inflamed tissue, whereas the levels of IL-22 and IL-22R were increased only in severely inflamed synovia. Anti-IL-22 treatment of IL-1Ra-/- mice significantly reduced the inflammation and bone erosion. Analysis of isolated single cells from the inflamed synovia revealed that IL-22 was mainly produced by IL-17-expressing T cells. CONCLUSION: These findings suggest that IL-22 plays an important role in IL-1-driven chronic joint destruction.
21488217 [Serum IL-18 levels in mice with collagen-induced arthritis treated by recombinant adenovi 2011 Mar OBJECTIVE: To investigate serum IL-18 levels in mice with collagen-induced arthritis treated by recombinant adenoviral vector containing mIL-18BP and mIL-4 fusion gene (AdmIL-18BP/mIL-4). METHODS: Arthritis was induced by injection of collagen in male DBA-1/BOM mice. Mice with collagen-induced arthritis (CIA) were intra-articularly injected with 10(7)pfu/6μL of AdmIL-18BP/mIL-4; and in mice of control groups AdLacZ or PBS were used. The animals were sacrificed at week 1, 2 and 4 after treatment. Serum IL-18 levels were determined by ELISA at the different time points. RESULT: The mean serum levels of IL-18 at weeks 1, 2, and 4 after injection of AdmIL-18BP/mIL-4 were (36.5±5.4)ng/L, (32.5 ± 3.2) ng/L and (28.7 ±2.9)ng/L, respectively, which were significantly lower than those at the same time point of AdLacZ group [(66.2 ±5.1)ng/L, (69.2 ±4.2)ng/L and (77.7 ±3.9)ng/L] and PBS group [(67.3 ±7.1)ng/L, (71.9 ±1.8)ng/L and (78.7±4.1)ng/L] (P<0.01 at all time points). In the therapy group, there were no significant differences in the mean serum concentrations of IL-18 at all time points. CONCLUSION: The serum IL-18 levels in CIA mice are down-regulated by treatment of recombinant adenovirus containing mIL-18BP and mIL-4 fuse gene, which might be a promising therapeutic strategy for rheumatoid arthritis.