Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
31466663 Juvenile Idiopathic Arthritis for the Pediatric Orthopedic Surgeon. 2019 Oct Juvenile idiopathic arthritis includes conditions characterized by joint inflammation of unknown etiology lasting longer than 6 weeks in patients younger than 16 years. Diagnosis and medical management are complex and best coordinated by a pediatric rheumatologist. The mainstay of therapy is anti-inflammatory and biologic medications to control pain and joint inflammation. Orthopedic surgical treatment may be indicated for deformity, limb length inequality, or end-stage arthritis. Evaluation of the cervical spine and appropriate medication management in consultation with a patient's rheumatologist are essential in perioperative care. Preoperative planning should take into account patient deformity, contracture, small size, osteopenia, and medical comorbidities.
31005039 Curcumin attenuates collagen-induced rat arthritis via anti-inflammatory and apoptotic eff 2019 Jul Curcumin is a natural herbal product that has been popularly used to treat autoimmune diseases in China; however, its effects on rheumatoid arthritis and its mechanism are not clear. The main purposes of this study are to explore the therapeutic effects of curcumin on collagen-induced arthritis (CIA) rats and the pharmacological mechanism. In the present study, CIA rats were established by injecting bovine type II collagen. Curcumin and methotrexate were then orally administered daily, and the swelling degree of the hind limb joints was scored every two days. Histopathological changes were observed by hematoxylin-eosin staining. The levels of cytokines (TNF-α, IL-1β, IL-17 and TGF-β) were detected by radioimmunoassay, while the expression of IκBα and COX-2 was detected by Western blot. In addition, cell viability was detected by CCK-8 assay, and the effect of curcumin on macrophage apoptosis was detected by flow cytometry and TUNEL assay. The results indicated that in vivo curcumin attenuated the degree of joint swelling of rats and the further development of joint histopathology. Moreover, it downregulated the levels of cytokines. In vitro curcumin inhibited the degradation of IκBα and reduced the production of COX-2 in LPS-induced inflammatory RAW264.7 cells. Importantly, curcumin significantly induced macrophage apoptosis. In conclusion, in this study, we have demonstrated that curcumin exerts therapeutic effects on arthritis in CIA rats and has a strong pharmacological activity on reducing the inflammatory response in macrophages. Its mechanism may be related to the inhibition of the NF-κB signaling pathway and the promotion of macrophage apoptosis.
30791646 Assessment of Cardiovascular Disease Risk and Therapeutic Patterns among Urban Black Rheum 2019 Feb 20 Rheumatoid arthritis (RA) patients have nearly twice the risk of cardiovascular disease (CVD) compared to the general population. We aimed to assess, in a predominantly Black population, the prevalence of traditional and RA-specific CVD risk factors and therapeutic patterns. Utilizing ICD codes, we identified 503 RA patients ≥18 years old who were seen from 2010 to 2017. Of them, 88.5% were Black, 87.9% were women and 29.4% were smokers. CVD risk factors (obesity, diabetes, hypertension, dyslipidemia) were higher than in previously reported White RA cohorts. Eighty-seven percent of the patients had at least one traditional CVD risk factor, 37% had three or more traditional CVD risk factors and 58% had RA-specific risk factors (seropositive RA, >10 years of disease, joint erosions, elevated inflammatory markers, extra-articular disease, body mass index (BMI) < 20). CV outcomes (coronary artery disease/myocardial infarction, heart failure, atrial fibrillation and stroke) were comparable to published reports. Higher steroid use, which increases CVD risk, and lesser utilization of biologics (decrease CV risk) were also observed. Our Black RA cohort had higher rates of traditional CVD risk factors, in addition to chronic inflammation from aggressive RA, which places our patients at a higher risk for CVD outcomes, calling for revised risk stratification strategies and effective interventions to address comorbidities in this vulnerable population.
31192789 [Pregnancy outcomes in Icelandic female patients with inflammatory arthritides. Nationwide 2019 Jun ntroduction: To collect nationwide data in Iceland on pregnancy and its outcomes among female patients with active inflammatory arthritides we linked two registers, the ICEBIO register and the Icelandic Medical Birth Register. METHODS: We used multivariate analysis to evaluate the risk of preterm birth, Caesarean section, low Apgar score at 5-minutes and low birth weight among females with inflammatory arthritis (rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS)) in comparison with healthy controls matched on age and parity. We also investigated pregnancies before and after the diagnosis of respective rheumatic disease and especially in respect to treatment with TNFα inhibitors (TNFi). RESULTS: In the end of 2016, 723 female patients were registered in ICEBIO as they had received treatment with TNFi due to inflammatory arthritis. Of those, 412 women had given birth to 801 children, whereof 597 were delivered before confirmed diagnosis of the mother and 53 were delivered after the start of the TNFi treatment. Relative risk of Caesarean section among these female with various arthritis conditions were 1.47 (95% CI: 1.19-1.82; p < 0,001) compared to controls and was highest in the group with PsA or 2.06 (1.41-3.02; p<0,001). We did not find increased risk of preterm delivery or low Apgar score. Patients with inflammatory arthritis had lower risk of children with low birth weight or 0.37 compared to healthy controls (95% CI: 0.36-0.37; p < 0.05). Due to low numbers of deliveries after the initiation of TNFi therapy (n=53) we were not able to perform any analysis for that group. CONCLUSION: Icelandic female patients with inflammatory arthritis are at an increased risk of Caesarean section in comparison to healthy controls. However, their newborns are in good condition and healthy at birth. Analysis of the impact of treatment with TNFi on pregnancy is not yet possible due to limited data.
31046162 Stem cells  from exfoliated  deciduous  teeth alleviate hyposalivation caused by Sjà 2019 Sep OBJECTIVES: To evaluate the effect of stem cells  from  exfoliated  deciduous  teeth on the hyposalivation caused by Sjögren syndrome (SS) and investigate the mechanism. METHODS: Stem cells were injected into the tail veins of non-obese diabetic mice, the animal model of SS. The saliva flow was measured after pilocarpine intraperitoneal injection. Apoptosis and autophagy were evaluated by TUNEL and Western blot. Lymphocyte proportions were detected by flow cytometer. RESULTS: Fluid secretion was decreased in 21-week-old mice. Stem cell treatment increased fluid secretion, alleviated inflammation in the submandibular glands and reduced inflammatory cytokine levels in the serum, submandibular glands and saliva. Stem cells decreased the apoptotic cell number and the expressions of ATG5 and Beclin-1 in the submandibular glands. Stem cells have no effect on other organs. Furthermore, the infused stem cells migrated to the spleen and liver, not the submandibular gland. Stem cells directed T cells towards Treg cells and suppressed Th1 and Tfh cells in spleen lymphocytes. CONCLUSION: Stem cells  from  exfoliated  deciduous  teeth alleviate the hyposalivation caused by SS via decreasing the inflammatory cytokines, regulating the inflammatory microenvironment and decreasing the apoptosis and autophagy. The stem cells regulated in T-cell differentiation are involved in the immunomodulatory effects.
31724510 The Emerging Role of Exosomal Non-coding RNAs in Musculoskeletal Diseases. 2019 Exosomes are phospholipid bilayer-enclosed membrane vesicles derived and constitutively secreted by various metabolically active cells. They are capable of mediating hetero- and homotypic intercellular communication by transferring multiple cargos from donor cells to recipient cells. Nowadays, non-coding RNAs (ncRNAs) have emerged as novel potential biomarkers or disease-targeting agents in a variety of diseases. However, the lack of effective delivery systems may impair their clinical application. Recently, accumulating evidence demonstrated that ncRNAs could be efficiently delivered to recipient cells using exosomes as a carrier, and therefore can exert a critical role in musculoskeletal diseases including osteoarthritis, rheumatoid arthritis, osteoporosis, muscular dystrophies, osteosarcoma and other diseases. Herein, we present an extensive review of biogenesis, physiological relevance and clinical implication of exosome-derived ncRNAs in musculoskeletal diseases.
30828233 Droxidopa for Hypotension of Different Etiologies: Two Case Reports. 2019 Mar Orthostatic hypotension is defined as a decrease in systolic blood pressure of at least 20 mmHg or a decrease in diastolic blood pressure of at least 10 mmHg (or both), within three minutes of moving from a supine to an upright or standing position. Droxidopa is a synthetic amino acid analog that is directly metabolized to norepinephrine by dopa-decarboxylase, subsequently providing alpha and beta-agonist effects to increase blood pressure. It is indicated in the treatment of neurogenic orthostatic hypotension caused by primary autonomic failure that is associated with Parkinson disease, multi-system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, and/or non-diabetic autonomic neuropathy. In addition, it has been studied in other disease states, such as diabetic autonomic neuropathy-associated orthostatic hypotension and supine hypotension. We report on two cases of off-label droxidopa use. The first case was for diabetic autonomic neuropathy-associated orthostatic hypotension, and the second case was for hypotension due to autonomic dysfunction associated with rheumatoid arthritis. Although the outcomes differed in each case, this article contributes to the literature demonstrating that droxidopa may have varying effects in treating orthostatic hypotension of non-neurogenic etiology.
31474860 Efficacy and Safety of Multiple Dosages of Fostamatinib in Adult Patients With Rheumatoid 2019 Background: Rheumatoid arthritis is a type of systemic and complex autoimmune other disease characterized by chronic joint inflammation. Spleen tyrosine kinase (Syk) inhibitors are regarded as an effective alternative to existing drugs for the treatment of this disease. However, studies evaluating fostamatinib, a new Syk inhibitor, are either invalid or insufficient. Through a systematic review and meta-analysis, we evaluated the efficacy and safety of fostamatinib at different dosages in rheumatoid arthritis patients that display an inadequate response to methotrexate or disease-modifying antirheumatic drugs. Methods: Randomized controlled trials published between January 2000 and November 2018 were retrieved from PubMed, Embase, Medline, Web of Science, and The Cochrane Library. We also searched a relevant website (www.clinicaltrials.gov) for retrieval of unpublished data. These studies compared different dosages of fostamatinib to placebo, including the intake of 100 mg fostamatinib twice per day (bid) for 4 weeks followed by 150 mg once per day (qd) vs. the intake of 100 mg bid. Results: Two investigators analyzed 11 randomized placebo-controlled trials consisting of 3,680 patients. Compared to placebo, fostamatinib resulted in an obvious reduction in the American College of Rheumatology 20% response standard [weighted mean difference (WMD) 1.96, 95% confidence interval (CI) [1.46, 2.61], P < 0.001] and disease activity score < 2.6 (WMD 4.70, 95% CI [3.14, 7.03], P < 0.001). Regarding safety, the incidence of serious adverse reactions was higher in the fostamatinib group than in the placebo group [risk ratio (RR) 2.10, 95% CI [1.57, 2.80], P < 0.001]. The same was true for other adverse events [RR 1.63, 95%CI [1.33, 2.01], P < 0.001]. Conclusions: Fostamatinib is an effective and safe therapeutic medicine administered to patients with rheumatoid arthritis over 24 weeks. It can alleviate the degree of swelling and inflammation of the joints. Furthermore, 100 mg bid can be considered the most beneficial regimen over a 24-week period. More data are however needed to clarify the incidence of other adverse events and serious adverse reactions.
31764904 Pharmacologic Management of Rheumatoid Arthritis. 2019 Nov/Dec Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune inflammatory disease of the joints, which can result in permanent cartilage and bone damage. Although the exact cause of RA is unknown, there are many risk factors that have been associated with RA. When RA occurs, the immune system mistakenly attacks healthy synovial and connective tissue. Available treatment options work to reduce inflammation or slow the disease progression. The American College of Rheumatology published guidelines for the treatment of rheumatoid arthritis in 2015, with an update expected in late 2019/early 2020. Nonpharmacologic therapy for patients with RA includes rest, occupational and physical therapy, and weight reduction and use of assistive devices, as necessary. Pharmacologic options include nonsteroidal anti-inflammatory drugs, corticosteroids, disease-modifying antirheumatic drugs, antitumor necrosis factor agents, and interleukin receptor antagonists.
31956457 A Missed Diagnosis of Bilateral Simultaneous Spontaneous Intracapsular Neck of Femur Fract 2019 Bilateral spontaneous simultaneous fractures of the neck of femurs are extremely rare, and only a few cases have been reported in literature. They are usually following high-energy trauma or may be due to an underlying pathological process such as frailty, osteomalacia, rickets, and chronic renal disease. They can also occur following epilepsy and electric shock. We report a 79-year-old gentleman who presented with sudden onset of bilateral hip pain with a background of rheumatoid arthritis and long-term steroid treatment. The bilateral hip fractures were missed initially and later presented with completely displaced fractures of the neck of femurs. He underwent a single-stage bilateral cemented hemiarthroplasty and made a good recovery. Bilateral simultaneous fractures of the hip in patients with rheumatoid arthritis have not been reported in literature so far, and the diagnosis can be easily overlooked. In patients with bilateral hip pain, one should have a high index of suspicion. Further appropriate cross-sectional imaging in the form of CT or MRI should also be considered.
31695699 Misunderstandings Between Platelets and Neutrophils Build in Chronic Inflammation. 2019 Regulated hemostasis, inflammation and innate immunity entail extensive interactions between platelets and neutrophils. Under physiological conditions, vascular inflammation offers a template for the establishment of effective intravascular immunity, with platelets providing neutrophils with an array of signals that increase their activation threshold, thus limiting collateral damage to tissues and promoting termination of the inflammatory response. By contrast, persistent systemic inflammation as observed in immune-mediated diseases, such as systemic vasculitides, systemic sclerosis, systemic lupus erythematosus or rheumatoid arthritis is characterized by platelet and neutrophil reciprocal activation, which ultimately culminates in the generation of thrombo-inflammatory lesions, fostering vascular injury and organ damage. Here, we discuss recent evidence regarding the multifaceted aspects of platelet-neutrophil interactions from bone marrow precursors to shed microparticles. Moreover, we analyse shared and disease-specific events due to an aberrant deployment of these interactions in human diseases. To restore communications between the pillars of the immune-hemostatic continuum constitutes a fascinating challenge for the near future.
31020239 Case report of an unusual and catastrophic presentation of coral reef aorta. 2019 Mar BACKGROUND: Coral reef aorta (CRA) is a rare condition characterized by atherosclerosis and overt calcification of the aorta leading to severe luminal stenosis of the vessel. Most patients present with hypertension and intermittent claudication at the time of diagnosis. Risk factors associated with this condition are essentially the same as those associated with atherosclerosis. However, no unique condition seems to predispose an individual to develop CRA. CASE SUMMARY: We describe the case of a patient known for rheumatoid arthritis (RA) treated with long-term systemic corticosteroids who presented with a shock of unknown aetiology and left ventricular ejection fraction of 10%. Conventional and computed tomography angiography showed a CRA with subtotal lesion of the aortic arch that led to cardiogenic shock. DISCUSSION: Even though the exact aetiology of her condition will remain uncertain, RA and extended use of corticosteroids likely played a role in the development of this severe form of CRA.
31607926 Sphingosine-1-Phosphate Receptor Subtype 1 (S1P1) Modulator IMMH001 Regulates Adjuvant- an 2019 Sphingosine-1-phosphate receptor subtype 1 (S1P(1)) is essential for lymphocyte egress from lymphoid organs into systemic circulation and provides a well-defined drug target for autoimmune disorders. IMMH001, also called SYL930, is a specific S1P(1)/S1P(4)/S1P(5) modulator. Here, we investigated the potential therapeutic effect of IMMH001 on rheumatoid arthritis (RA). IMMH001 rendered periphery blood lymphocytes insensitive to the egress signal from secondary lymphoid organs. Importantly, in both rat adjuvant-induced arthritis and collagen-induced arthritis models, IMMH001 treatment significantly inhibited the progression of RA and RA-associated histological changes in the joints of Sprague-Dawley rats, including hind paw swelling and arthritic index, and thus reduced the pathological score. Furthermore, IMMH001 markedly decreased proinflammatory cytokine and chemokine release from the damaged joints. These data demonstrated that IMMH001 is a promising drug candidate for RA treatment.
30642121 Anti-Arthritis Effect through the Anti-Inflammatory Effect of Sargassum muticum Extract in 2019 Jan 13 (1) Background: Rheumatoid arthritis is a chronic autoimmune disease that causes progressive articular damage and functional loss. It is characterized by synovial inflammation that leads to progressive cartilage destruction. For this reason, research on functional foods that reduce the inflammatory response are under progress. (2) Methods: We focused on the anti-inflammatory effects of Sargassum muticum, and confirmed the effect of the extract on the collagen-induced arthritis (CIA) DBA/1J mice model. (3) Results: The extract was given at concentrations of 50, 100, and 200 mg/kg, and the arthritis score and edema volume of the experimental group were significantly different from the CIA group. The level of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were determined in serum and lymphocytes. The expression of these cytokines in the serum remarkably decreased from S. muticum extract (SME)100 mg/kg, and decreased from SME 200 mg/kg in lymphocytes. Also, immunohistochemical analysis of IL-6 and TNF-α in the joints revealed that the inflammatory response was noticeably lower when treated with S. muticum extract. (4) Conclusions: This study provides results of the experiment of S. muticum extract treatment in a mouse model. The treatment was found to contribute to the alleviation of edema and symptoms by reducing the expression of inflammatory cytokines. It was concluded that it may be a useful substance to help in the mitigation of arthritis symptoms.
31426562 Differential Expression Profiles of the Transcriptome and miRNA Interactome in Synovial Fi 2019 Aug 18 Using next-generation sequencing to decipher the molecular mechanisms underlying aberrant rheumatoid arthritis synovial fibroblasts (RASF) activation, we performed transcriptome-wide RNA-seq and small RNA-seq on synovial fibroblasts from rheumatoid arthritis (RA) subject and normal donor. Differential expression of mRNA and miRNA was integrated with interaction analysis, functional annotation, regulatory network mapping and experimentally verified miRNA-target interaction data, further validated with microarray expression profiles. In this study, 3049 upregulated mRNA and 3552 downregulated mRNA, together with 50 upregulated miRNA and 35 downregulated miRNA in RASF were identified. Interaction analysis highlighted contribution of miRNA to altered transcriptome. Functional annotation revealed metabolic deregulation and oncogenic signatures of RASF. Regulatory network mapping identified downregulated FOXO1 as master transcription factor resulting in altered transcriptome of RASF. Differential expression in three miRNA and corresponding targets (hsa-miR-31-5p:WASF3, hsa-miR-132-3p:RB1, hsa-miR-29c-3p:COL1A1) were also validated. The interactions of these three miRNA-target genes were experimentally validated with past literature. Our transcriptomic and miRNA interactomic investigation identified gene signatures associated with RASF and revealed the involvement of transcription factors and miRNA in an altered transcriptome. These findings help facilitate our understanding of RA with the hope of serving as a springboard for further discoveries relating to the disease.
30988705 Inhibitory effect of tanshinone IIA on inflammatory response in rheumatoid arthritis throu 2019 May The current study aimed to investigate the inhibitory effect of tanshinone IIA (Tan IIA) on the inflammatory response in patients with rheumatoid arthritis (RA) and explore its mechanism. A total of 50 patients with RA were randomly separated into the control group (15 cases) and the research group (35 cases). The tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels in serum were determined, and peripheral blood mononuclear cells (PBMCs) were separated from patients with RA and cultured in vitro. The effects of the β-arrestin 2 small interfering (si)RNA incubation, lipopolysaccharide (LPS) stimulation or Tan IIA incubation on TNF-α and IL-6 levels, and the expression levels of β-arrestin 2, NAD-dependent protein deacetylase sirtuin-1 (SIRT1) and transcription factor p65 (p65) proteins were investigated. Prior to treatment, no significant differences in TNF-α and IL-6 levels in serum of patients with RA were identified between the research and control groups. Following treatment, the TNF-α and IL-6 levels in the serum of patients with RA in the research group were significantly lower compared with those in the research group prior to treatment and those in the control group following treatment (P<0.05). Tan IIA inhibited the LPS-induced secretion of TNF-α and IL-6, upregulated the LPS-inhibited expression of the β-arrestin 2 and SIRT1 proteins, and downregulated the LPS-induced expression of the p65 protein in the PBMCs of patients with RA. The β-arrestin 2 small interfering (si)RNA significantly upregulated the secretion of TNF-α and IL-6, inhibited the expression of the SIRT1 protein and upregulated the expression of the p65 protein in PBMCs of patients with RA. Tan II A effectively increased the weight of rats with rheumatoid arthritis, and reduced the circumference of the left posterior ankle, the posterior plantar metatarsal thickness, and the content of serum TNF-α and IL-6. Tan IIA did not significantly reverse these β-arrestin 2 siRNA-induced changes. Tan IIA inhibited the inflammatory response in PBMCs of patients with RA by upregulating β-arrestin 2 expression.
30858947 Serum YKL-40 levels and disease characteristics in patients with rheumatoid arthritis. 2019 Winter BACKGROUND: The present study aimed to evaluate serum YKL-40 levels in patients with rheumatoid arthritis (RA) compared to healthy subjects and to search whether there is an association between YKL-40 levels and disease characteristics in RA. METHODS: In this cross-sectional study, 60 RA patients based on the ACR/EULAR 2010 criteria and 30 age- and sex-matched healthy controls were included. In patients, clinical examination was performed and disease activity score 28 (DAS-28) measure of disease activity was assessed. Serum YKL-40 level was measured using ELISA kit. RESULTS: The mean±SD age of patients and controls was 54.86±11.65 and 50.71±3.72 years, respectively). Serum YKL-40 level was significantly higher in RA patients (951.63±639.98 pg/mL) compared to healthy controls (444.92±150.37 pg/mL) (P<0.001). There was no significant difference in serum YKL-40 level according to the activity of disease (p>0.05). There were significant positive correlations between serum YKL-40 level with disease activity (r=0.347, P=0.007) and rheumatoid factor (r=0.396, P=0.002). There were no significant correlations between serum YKL-40 level with demographic characteristics as well as biochemical measurements including serum creatinine, blood urea nitrogen, erythrocyte sedimentation rate, C-reactive protein and anti-cyclic citrullinated peptide. CONCLUSION: Our study revealed higher serum YKL-40 levels in RA patients compared to healthy controls, which correlated positively with disease activity. Therefore, YKL-40 can be considered as a novel biomarker for disease activity estimation in RA.
30891314 Studying the effects of haplotype partitioning methods on the RA-associated genomic result 2019 Jul The human genome, which includes thousands of genes, represents a big data challenge. Rheumatoid arthritis (RA) is a complex autoimmune disease with a genetic basis. Many single-nucleotide polymorphism (SNP) association methods partition a genome into haplotype blocks. The aim of this genome wide association study (GWAS) was to select the most appropriate haplotype block partitioning method for the North American Rheumatoid Arthritis Consortium (NARAC) dataset. The methods used for the NARAC dataset were the individual SNP approach and the following haplotype block methods: the four-gamete test (FGT), confidence interval test (CIT), and solid spine of linkage disequilibrium (SSLD). The measured parameters that reflect the strength of the association between the biomarker and RA were the P-value after Bonferroni correction and other parameters used to compare the output of each haplotype block method. This work presents a comparison among the individual SNP approach and the three haplotype block methods to select the method that can detect all the significant SNPs when applied alone. The GWAS results from the NARAC dataset obtained with the different methods are presented. The individual SNP, CIT, FGT, and SSLD methods detected 541, 1516, 1551, and 1831 RA-associated SNPs respectively, and the individual SNP, FGT, CIT, and SSLD methods detected 65, 156, 159, and 450 significant SNPs respectively, that were not detected by the other methods. Three hundred eighty-three SNPs were discovered by the haplotype block methods and the individual SNP approach, while 1021 SNPs were discovered by all three haplotype block methods. The 383 SNPs detected by all the methods are promising candidates for studying RA susceptibility. A hybrid technique involving all four methods should be applied to detect the significant SNPs associated with RA in the NARAC dataset, but the SSLD method may be preferred because of its advantages when only one method was used.
30528734 Eosinophils attenuate arthritis by inducing M2 macrophage polarization via inhibiting the 2019 Jan 15 Rheumatoid arthritis (RA) represents a type of autoimmune disease that mainly affect the joints due to persistent synovitis. Eosinophils were Th2 effector cells that have been shown to have anti-inflammatory role recently. In this study, we aimed to investigate the effects of eosinophils transfer on arthritis and underlying mechanisms. DBA/1 mice were induced with collagen-induced arthritis (CIA) and treated with purified eosinophils at different time points. We showed that eosinophils transfer attenuated arthritis in CIA mice. Meanwhile, TNF-α, IL-6, IL-12 and iNOS levels were decreased whereas TGF-β, IL-10, IL-13 and Arg1 levels were increased after eosinophil transfer. In vitro stimulation of bone marrow-derived macrophage (BMDM) with LPS and IFN-γ induced high expression of CD68, iNOS, TNF-α, IL-6, and IL-12, while treatment with eosinophils downregulated their expression levels. Furthermore, high levels of p-IκB and p-P38 expression in BMDM induced by LPS and IFN-γ could be suppressed by eosinophil treatment, and a P38 or IκB inhibitor accelerated the effect of eosinophils on macrophage polarization. Our results demonstrate that eosinophils exert anti-inflammatory effects in arthritis by inducing M2 macrophage polarization via inhibiting the IκB/P38 MAPK signaling pathway.
31028049 Complex presentation of adult-onset Still's disease. 2019 Apr 25 A 61-year-old woman was admitted with feeling generally unwell with influenza-like symptoms, for almost a month. This was followed by dyspnoea, productive cough and fever of >40°C. She was started on oral antibiotics in community, but due to rising inflammatory markers, she was referred for admission to our hospital. Chest X-ray showed left basal pneumonia and SE was started on intravenous antibiotics according to microbiologist's advice. During admission she developed deranged liver functions with right upper quadrant tenderness, pleural and pericardial effusions. This was followed by multiple joint aches, mouth ulcers and a rash on her chest. Finally, after several days and clinical dilemma, she was diagnosed with adult-onset Still's disease by the rheumatologist and was started on prednisolone, to which she showed marked improvement, and was later maintained on methotrexate and hydrotherapy. She was in remission during her follow-up in the rheumatology clinic.