scholarly journals POS0346 THE THERAPEUTIC EFFECTS OF OMEGA-6 PUFA (PINOLENIC ACID) ON THE TRANSCRIPTOMIC PROFILE OF ACTIVATED PERIPHERAL BLOOD MONONUCLEAR CELLS ISOLATED FROM HEALTHY CONTROLS AND RHEUMATOID ARTHRITIS PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 402-403
Author(s):  
R. Takala ◽  
D. Ramji ◽  
R. Andrews ◽  
Y. Zhou ◽  
J. Burston ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatic Diseases ◽  
Pathway Analysis ◽  
Healthy Controls ◽  
Pinolenic Acid ◽  
Eular Recommendations ◽  
Tnf Α ◽  
Omega 6 ◽  
Disease Modifying ◽  
Anti Inflammatory

Background:Globally, Rheumatoid arthritis (RA) is the most common chronic inflammatory arthritis. EULAR recommends patient education and disease modifying anti-rheumatic drugs including advanced targeted therapies for management1 2. Many patients seek advice on a dietary intervention that may improve symptoms. Foods high in omega-3 polyunsaturated fatty acids (PUFAs) is one of the most common recommended based on their anti-inflammatory properties3 4. Previously we showed pinolenic acid (PNLA), an omega-6 (PUFAs) found in pine nuts, reduced lipid uptake, endocytosis and migration of monocyte in vitro. PNLA also reduced IL-6, TNF-α, IL-1β and PGE2 produced by lipopolysaccharide (LPS) activated PBMCs from patients with RA and healthy controls (HCs).Objectives:We hypothesis that PNLA inhibits key inflammatory processes in synovities as in diagram.1. We investigated the transcriptomic profile of PNLA treatment on LPS activated PBMCs isolated from HCs and RA patients.Methods:Adult RA patients (n=6) were recruited from the Rheumatology Department of University Hospital of Wales together with 6 HCs. Blood was collected after taking signed informed consent. PBMCs were isolated by Ficoll gradient centrifugation and pre-treated with 25 μM PNLA or vehicle and then activated with 100 ng/ml LPS. RNA was extracted followed by library construction and sequencing for whole genomic transcriptome. DEGs were analysed using DESeq2 and pathway analysis was performed using Ingenuity pathway analysis. The study was approved by the Research Ethics Committee for Wales (reference no. 12/WA/0045).Results:DEGs were selected with at least differential genes using at least 1.2* fold changes and adjusted p-value of <0.05. PNLA significantly upregulates the expression of PDK4, PAI-1 (SERPINE1), FBP1, and NDRG2. These genes have important roles in metabolic pathways. Pathway analysis predicted upstream activation of nuclear receptors peroxisome proliferator-activated receptor (PPARs) involved in the anti-inflammatory process, and inhibition of NF-κB and STAT1, the major transcription factors of the pro-inflammatory cytokines TNF-α, IL-1, IL-6 and IFN-γ.Conclusion:PNLA has significant effects on the regulation of metabolic and inflammatory pathways in PBMCs from RA patients and HCs. Based on these results we demonstrate that PNLA may have beneficial anti-inflammatory effects in patients with RAReferences:[1]Agca R, Heslinga SC, Rollefstad S, Heslinga M, McInnes. IB, Peters MJL, Kvien, TK., Dougados, M, Radner, H, Atzeni, F. and Primdahl, J. 2017. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Annals of the rheumatic diseases, 76(1), pp.17-28.[2]Smolen JS, Landewé RBM, Bijlsma JWJ, et al. 2019. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: updateAnnals of the Rheumatic Diseases 2020; 79:685-699.[3]Chehade L, Jaafar ZA, El Masri D, Zmerly H, Kreidieh D, Tannir H, Itani L, and El Ghoch, M. 2019. Lifestyle Modification in Rheumatoid Arthritis: Dietary and Physical Activity Recommendations Based on Evidence. Current rheumatology reviews, 15(3), pp.209-214.[4]Marchand NE, Chiu Y-H, Yoshida K, Malspeis S, Sparks JA, Costenbader K, et al. Threshold Level for Long-term Healthy Diet Adherence to Reduce the Risk of Rheumatoid Arthritis Among Women in a Prospective Cohort Using a Marginal Structural Model Approach.:25.Diagram 1.Disclosure of Interests:None declared

scholarly journals Pinolenic acid Mediated Anti-inflammatory and Immunometabolic Effects in Peripheral blood-derived Monocytes from patients with Rheumatoid Arthritis is Associated with Modulation of miRNA expression

2022 ◽  
Author(s):  
Rabaa Takala ◽  
Dipak Ramji ◽  
Robert Andrews ◽  
You Zhou ◽  
Mustafa Farhat ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mitochondrial Dysfunction ◽  
Pathway Analysis ◽  
Peripheral Blood ◽  
Interleukin 1 ◽  
Pyruvate Dehydrogenase Kinase ◽  
Metabolic Effects ◽  
Pinolenic Acid ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Objectives: Pinolenic acid (PNLA), an omega-6 polyunsaturated fatty acid from pine nuts, has anti-inflammatory and anti-atherogenic effects. We aimed to investigate the actions of PNLA on activated purified monocytes from peripheral blood of patients with rheumatoid arthritis (RA).Methods: Flow cytometry was used to assess the intracellular expression of TNF-α, IL-6, IL-1β, and IL-8 in purified monocytes from patients with RA after lipopolysaccharide (LPS) stimulation with/without PNLA pre-treatment. The whole genomic transcriptomic (WGT) profile of PNLA-treated, and LPS-activated monocytes from patients with active RA was investigated by RNA-sequencing.Results: PNLA reduced percentage of monocytes expressing the cytokines TNF-α by 23% (p=0.048), IL-6 by 25% (p=0.011), IL-1β by 23% (p=0.050) and IL-8 by 19% (p=0.066). Canonical pathway analysis showed that PNLA inhibited oxidative phosphorylation (p= 9.14E-09) and mitochondrial dysfunction (p=4.18E-08), while the sirtuin (SIRTs) signalling pathway was activated (p=8.89E-06). Pathway analysis predicted upstream activation of peroxisome proliferator-activated receptors (PPARs), sirtuin3, and let7miRNA, which are anti-inflammatory and antioxidative. In contrast, DAP3, LIF and STAT3, which are involved in TNF-α, and IL-6 signal transduction, were inhibited. Many miRNAs were modulated by PNLA suggesting potential post-transcriptional regulation of metabolic and immune response that has not been described previously. Multiple miRNAs target pyruvate dehydrogenase kinase-4 (PDK4), single-immunoglobulin interleukin-1 receptor-related molecule (SIGIRR), mitochondrially encoded ATP synthase membrane subunit 6 (MT-ATP6) and acetyl-CoA acyltransferase 2 (ACAA2); genes implicated in cell metabolism, inflammation, and mitochondrial dysfunction.Conclusion: PNLA has anti-inflammatory and immune-metabolic effects on monocytes that are pathogenic in RA and atherosclerosis. Dietary PNLA supplementation may regulate key miRNAs that are involved in mitochondrial, metabolic, and inflammatory pathways.

scholarly journals P201 Anti-inflammatory and immunologic actions of pinolenic acid in rheumatoid arthritis

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Rabaa Takala ◽  
Dipak Ramji ◽  
Ernest Choy
Keyword(s):  
Rheumatoid Arthritis ◽  
Flow Cytometry ◽  
Mononuclear Cells ◽  
Vehicle Control ◽  
Boyden Chamber ◽  
Pinolenic Acid ◽  
Human Macrophages ◽  
Monocyte Migration ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Background Rheumatoid arthritis (RA) is a common inflammatory arthritis. Although advanced targeted therapies have improved prognosis, many patients seek advice on dietary intervention that may improve symptoms. Pinolenic acid (PNLA) is a polyunsaturated fatty acid found in pine nuts. We investigated the anti-inflammatory effects of 25-100 μM PNLA on cell line, primary culture, and peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy controls (HCs). Methods 1- Migration using modified Boyden Chambers: THP-1 monocytes incubated with vehicle or PNLA were added to the apical compartment of a modified Boyden chamber. The migration of the cells through inserts of 8 μm pore size in response to the chemokine monocyte chemoattractant protein-1 (MCP-1) added to basolateral (bottom) chamber was determined. 2- Macropinocytosis using Lucifer yellow (LY): THP-1 and primary human macrophages were pre-incubated with PNLA or vehicle control followed by LY. After incubation, cells were removed, fixed and assessed by flow cytometry. 3- Lipid uptake using Dil-oxidised low-density lipoprotein (Dil-oxLDL): THP-1 and primary macrophages were pre-incubated with PNLA or vehicle control followed by Dil-oxLDL. After incubation, cells were removed, fixed and assessed by flow cytometry. 4- Cytokines release by lipopolysaccharide (LPS) stimulated PBMCs: PBMCs were isolated from blood obtained from RA patients aged ≥18 years and HCs. Monocytes were purified and cultured with PNLA or vehicle control. Cells were stimulated with LPS. IL-6, TNF-α, IL-1β and prostaglandin E2 (PGE2) in the supernatant were assessed by ELISAs. For macrophages, monocytes were left to grow and differentiate over 10 days, the differentiated macrophages were treated with PNLA or vehicle and activated with LPS and assayed in identical conditions for monocytes. Results PNLA at all concentrations reduced THP-1 monocytes migration by average of 55% (p &lt; 0.001) when compared with vehicle controls. Macropinocytosis of THP-1 macrophages and human macrophages were reduced by almost 50% (p &lt; 0.001) and 45% (p &lt; 0.001) respectively by PNLA. Similarly, Dil-oxLDL uptake by THP-1 macrophages and primary macrophages were reduced by 40% (p &lt; 0.01) and 25% (p &lt; 0.05) respectively by 25 μM PNLA. Release of IL-6 and TNF-α by LPS stimulated monocytes in RA patients were reduced with 25 and 50 μM PNLA by 60% (p &lt; 0.001) and in HC by 50% and 35% respectively (p &lt; 0.01). PGE2 levels were inhibited by the same percentage in both HC and RA monocytes (p &lt; 0.001) by 50 μM PNLA. Similarly, effects were observed with IL-6, TNF- α, and PGE2 levels in LPS-stimulated macrophages especially in RA patients 30% (p &lt; 0.05). Conclusion Our data suggest that PNLA significantly attenuated monocyte migration, significantly reduced macropinocytosis and Dil-oxLDL uptake in macrophages. Furthermore, PNLA inhibited production of IL-6, TNF-α and PGE2 levels in LPS-stimulated monocytes and macrophages from RA patients. These data inform on the potential anti-inflammatory and analgesic effects of PNLA. Disclosures R. Takala None. D. Ramji None. E. Choy None.

Circulating Dickkopf-1 Is Correlated with Bone Erosion and Inflammation in Rheumatoid Arthritis

2011 ◽  
Vol 38 (5) ◽  
pp. 821-827 ◽  
Author(s):  
SHI-YAO WANG ◽  
YAN-YING LIU ◽  
HUA YE ◽  
JIAN-PING GUO ◽  
RU LI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatic Diseases ◽  
Bone Erosion ◽  
Interleukin 1 ◽  
Healthy Controls ◽  
Serum Samples ◽  
Reactive Protein ◽  
Tnf Α ◽  
Factor Α ◽  
Dickkopf 1

Objective.To explore the potential role of Dickkopf-1 (DKK-1) in rheumatoid arthritis (RA) and to evaluate the effect of a tumor necrosis factor-α (TNF-α) inhibitor (infliximab) and an interleukin 1 receptor antagonist (IL-1Ra; anakinra) on DKK-1 secretion in patients with RA.Methods.Serum samples were collected from 100 patients with RA, 100 patients with other rheumatic diseases (e.g., osteoarthritis and ankylosing spondylitis), and 40 healthy controls. DKK-1 and osteoprotegerin (OPG) levels in serum were detected by ELISA. Serum C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), rheumatoid factor (RF) titers, and anti-cyclic citrullinated peptide antibody were also measured in patients with RA.Results.The serum level of DKK-1 was significantly higher in patients with RA than in healthy controls and those with other rheumatic diseases (p < 0.01); the serum DKK-1 level was correlated with levels of CRP (r = 0.488, p = 0.003) and ESR (r = 0.458, p = 2.4 x 10−4) and the Sharp score of radiologic change (r = 0.449, p = 0.001) in RA. In contrast to the increasing level of OPG, DKK-1 was significantly decreased in RA patients treated with TNF-α inhibitor (p < 0.01). DKK-1 was significantly decreased in RA patients treated with IL-1Ra (p < 0.01).Conclusion.DKK-1, as an important mediator, was correlated with bone erosion and inflammation in RA. The change of DKK-1 level may serve as a biomarker of disease activity and bone erosion.

scholarly journals CO0005 C-C CHEMOKINE RECEPTOR TYPE 5 AND ITS LIGANDS CCL4, 8 AND 11 CAN LINK COVID-19, RHEUMATOID ARTHRITIS AND HYDROXYCHLOROQUINE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 213.3-214
Author(s):  
M. Y. Hachim ◽  
S. Hannawi
Keyword(s):  
Rheumatoid Arthritis ◽  
Mechanism Of Action ◽  
Immune Cells ◽  
Health Concern ◽  
Healthy Controls ◽  
Global Public Health ◽  
Ccr5 Expression ◽  
Disease Modifying Drugs ◽  
Link Type ◽  
Disease Modifying

Background:Coronavirus disease (COVID-19) caused by SARS-COV2 represents an unprecedented global public health concern with a particular burden on patients with chronic diseases and those on immune-modulating drugs. It is especially worrisome to patients with rheumatoid arthritis (RA) who are on immune suppression regimens[1]. On the other side, many reports showed and recommended the use of some Disease-Modifying Drugs commonly used to treat rheumatic diseases like hydroxychloroquine. However, the general understanding of COVID-19 characteristics in this population and the mechanism of action of these drugs in COVID-19 is still unknown[2].Objectives:Explore publicly available transcriptomic dataset of patients infected with SARS-COV2 compared to uninfected to identify differentially expressed genes (DEGs) related to the immune system that might be pathogenic in RA synovium. Then explore the effect of Disease-Modifying Drugs on their local expression that might give hints about their possible mechanism of action.Methods:RNAseq dataset (GSE147507) were retrieved using the Gene Expression Omnibus (GEO) and used to identify DEGs between infected and uninfected lung samples using BioJupies tools [3]. The DEGs were explored for common pathways using Metascape online tool (http://metascape.org) [10], as shown in figure (1). The chemokines genes were filtered out, and their common receptor (CR) was identified. The immune cells that express a higher level of the identified receptor were explored using DICE project tool (https://dice-database.org/). The expression of CR was searched in a microarray dataset (GSE77298) of synovial biopsies of RA and healthy controls. RNAseq dataset (GSE97165) of synovial biopsies taken from 19 early RA patients at baseline and after six months of Triple Disease-Modifying Anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine, and hydroxychloroquine) treatment.Results:84 DEGs were identified between uninfected and COVID-19 infected lung samples. These DEGs were enriched in pathways specific to (response to the virus, response to interferon, leukocyte activation, and chemotaxis). Interestingly, SARS-COV-2 infected lungs express more CCL4, CCL8, and CCL11; the three ligands shared the same receptor, which is CCR5. Top immune cells that express CCR5 were CD4 T memory T reg cells, Th17, Th1, and monocytes. CCR5 was significantly upregulated in RA compared to healthy controls synovium (p=0.04) and was dramatically downregulated after six months of tDMARD treatment (p=0.004), as shown in figure (2).Conclusion:Using publicly available transcriptomic datasets properly highlighted the possible beneficiary effect of DMARDs in patients with COVID-19, which can block CCR5 rich immune cells recruitment.References:[1]Favalli, E.G., et al.,COVID-19 infection and rheumatoid arthritis: Faraway, so close!Autoimmun Rev, 2020. 19(5): p. 102523.[2]Gianfrancesco, M.A., et al.,Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries.The Lancet Rheumatology, 2020. 2(5): p. e250-e253.[3]Torre, D., A. Lachmann, and A. Ma’ayan,BioJupies: Automated Generation of Interactive Notebooks for RNA-Seq Data Analysis in the Cloud.Cell Systems, 2018. 7(5): p. 556-561.e3.Figure 1.Flowchart of transcriptomic analysisFigure 2.(A) Top immune cells that express CCR5 (B) CCR5 expression in synovial biopsies of RA and control (C) CCR5 expression at baseline and after 6 months of tDMARD treatment.Disclosure of Interests:None declared

scholarly journals FRI0651-HPR A RANDOMIZED PROSPECTIVE OPEN-LABEL CONTROLLED TRIAL COMPARING THE PERFORMANCE OF A CONNECTED MONITORING INTERFACE IN PATIENTS WITH RHEUMATOID ARTHRITIS VERSUS PHYSICAL ROUTINE MONITORING

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 929.1-930
Author(s):  
Y. M. Pers ◽  
V. Valsecchi ◽  
T. Mura ◽  
S. Aouinti ◽  
N. Filippi ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Rheumatic Diseases ◽  
Tight Control ◽  
Link Type ◽  
Functional Scores ◽  
Monitoring Group ◽  
Disease Modifying

Background:Telemedicine has found wider application in chronic diseases for encouraging tight home-monitoring in order to improve patients’ outcome (Smolen et al. 2017).In previous studies, a high feasibility and high patient-satisfaction rate was found as well as the evidence for a superior or equal effectiveness of telemedicine compared to the standard face-to-face approach, however the results were weakened by some methodological biases and wide heterogeneity of interventions, thus preventing to draw definitive conclusions (Piga et al. 2017; Najm, Gossec, et al. 2019).Objectives:In rheumatoid arthritis (RA), telemedicine may allow a tight control of disease activity while reducing hospital visits. We developed a smartphone application connected with a physician’s interface to monitor RA patients. We aimed to assess the performance of this e-Health solution in comparison with routine practice in the management of patients with RA.Methods:A 6-month pragmatic, randomized, controlled, prospective, clinical trial was conducted in RA patients with high to moderate disease activity starting a new Disease Modifying Anti-Rheumatic Drug (DMARD) therapy. Two groups were established: “connected monitoring” and “conventional monitoring”. The primary outcome was the number of physical visits between baseline and 6 months. Secondary outcomes included adherence, satisfaction, changes in clinical, functional, and health status scores (SF-12).Results:Of the 94 randomized patients, 89 completed study: 44 in the “conventional monitoring” arm and 45 in the “connected monitoring” arm. The total number of physical visits between baseline and 6 month was significantly lower in the “connected monitoring” group (0.42 ± 0.58 versus 1.93 ± 0.55; p<0.05). No differences between groups were observed in the clinical and functional scores. A better quality of life for SF-12 subscores (Role-Physical, Social-Functioning and Role-Emotional) were found in the “connected monitoring” group.Conclusion:According to our results, a connected monitoring reduces the number of physical visits while maintaining a tight control of disease activity and improving quality of life in patients with RA starting a new treatment.References:[1] Najm, Aurelie, Laure Gossec, Catherine Weill, David Benoist, Francis Berenbaum, and Elena Nikiphorou. 2019. “Mobile Health Apps for Self-Management of Rheumatic and Musculoskeletal Diseases: Systematic Literature Review.”JMIR MHealth and UHealth7 (11): e14730.https://doi.org/10.2196/14730.[2] Piga, Matteo, Ignazio Cangemi, Alessandro Mathieu, and Alberto Cauli. 2017. “Telemedicine for Patients with Rheumatic Diseases: Systematic Review and Proposal for Research Agenda.”Seminars in Arthritis and Rheumatism47 (1): 121–28.https://doi.org/10.1016/j.semarthrit.2017.03.014.[3] Smolen, Josef S, Robert Landewe, Johannes Bijlsma, Gerd Burmester, Katerina Chatzidionysiou, Maxime Dougados, Jackie Nam, et al. 2017. “EULAR Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs: 2016 Update.”Annals of the Rheumatic Diseases76 (6): 960–77.https://doi.org/10.1136/annrheumdis-2016-210715.Disclosure of Interests:None declared

scholarly journals Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway

2017 ◽  
Vol 43 (2) ◽  
pp. 540-552 ◽  
Author(s):  
Hany H. Arab ◽  
Samir A. Salama ◽  
Tamer M. Abdelghany ◽  
Hany A. Omar ◽  
El-Shaimaa A. Arafa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mapk Pathway ◽  
Lipid Peroxide ◽  
Mitogen Activated Protein Kinase ◽  
Camel Milk ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory

Background/Aims: Camel milk (CM) has shown beneficial anti-inflammatory actions in several experimental and clinical settings. So far, its effect on rheumatoid arthritis (RA) has not been previously explored. Thus, the current work aimed to evaluate the effects of CM in Adjuvant-induced arthritis and air pouch edema models in rats, which mimic human RA. Methods: CM was administered at 10 ml/kg orally for 3 weeks starting on the day of Freund’s adjuvant paw inoculation. The levels of TNF-α and IL-10 were measured by ELISA while the protein expression of NF-κBp65, COX-2 and iNOS was detected by immunohistochemistry. The expression of MAPK target proteins was assessed by Western blotting. Results: CM attenuated paw edema, arthritic index and gait score along with dorsal pouch inflammatory cell migration. CM lowered the TNF-α and augmented the anti-inflammatory IL-10 levels in sera and exudates of arthritic rats. It also attenuated the expression of activated NF-κBp65, COX-2 and iNOS in the lining of the dorsal pouch. Notably, CM inhibited the MAPK pathway signal transduction via lowering the phosphorylation of p38 MAPK, ERK1/2 and JNK1/2 in rat hind paws. Additionally, CM administration lowered the lipid peroxide and nitric oxide levels and boosted glutathione and total anti-oxidant capacity in sera and exudates of animals. Conclusion: The observed CM downregulation of the arthritic process may support the interest of CM consumption as an adjunct approach for the management of RA.

scholarly journals Interleukin-37 as an anti-inflammatory cytokine: does its relation to disease activity suggest its potential role in rheumatoid arthritis therapy?

2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Eman A. Baraka ◽  
Mona G. Balata ◽  
Shereen H. Ahmed ◽  
Afaf F. Khamis ◽  
Enas A. Elattar
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Cross Sectional Study ◽  
Healthy Controls ◽  
Tender Joint ◽  
Cross Sectional ◽  
Reactive Protein ◽  
Significant Difference ◽  
The Mean ◽  
Anti Inflammatory

Abstract Background This study aimed to measure the serum and synovial interleukin (IL)-37 levels in rheumatoid arthritis (RA) patients compared to patients with primary knee osteoarthritis (PKOA) and healthy controls and to detect its relation to RA disease activity. Results This cross-sectional study included 50 RA patients with a mean age of 40.24 ± 8.62 years, 50 patients with PKOA with a mean age of 56.69 ± 4.21, and 40 healthy controls with a mean age of 41.75 ± 7.38 years. The mean serum IL-37 level in the RA patients (382.6 ± 73.97 pg/ml) was statistically significantly (P < 0.001) the highest among the studied groups; however, it showed a non-significant difference between the PKOA patients (70.38 ± 27.49 pg/ml) and the healthy controls (69.97 ± 25.12 pg/ml) (P > 0.94). Both serum and synovial IL-37 levels were significantly positively correlated with disease activity scores (r = 0.92, P< 0.001 and r = 0.85, P < 0.001), tender joint counts (r = 0.83, P < 0.001 and r = 0.82, P < 0.001 ), swollen joint counts (r = 0.72, P < 0.001 and r = 0.60, P < 0.001), visual analog scale (r = 0.82, P < 0.001 and r = 0.82, P < 0.001), erythrocyte sedimentation rate (r = 0.75, P < 0.001 and r = 0.65, P < 0.001), and C-reactive protein (r = 0.93, P < 0.001 and r = 0.79, P < 0.001), respectively. Conclusion Serum and synovial IL-37 were significantly elevated in the RA patients, and they were closely correlated. Being less invasive, the serum IL-37 could be a marker of disease activity and could reflect the effective disease control by drugs. Having an anti-inflammatory effect could not suggest IL-37 as the key player to control inflammation alone, but its combination with other anti-proinflammatory cytokines could be investigated.

Levels of Plasma-soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) Are Correlated with Disease Activity in Rheumatoid Arthritis

2012 ◽  
Vol 39 (5) ◽  
pp. 933-938 ◽  
Author(s):  
SANG TAE CHOI ◽  
EUN-JIN KANG ◽  
YOU JUNG HA ◽  
JUNG-SOO SONG
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Myeloid Cells ◽  
Disease Status ◽  
Joint Disease ◽  
Healthy Controls ◽  
Cell Counts ◽  
Tnf Α ◽  
White Blood Cell Counts ◽  
Factor Α

Objective.To determine whether levels of plasma-soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) are elevated in patients with rheumatoid arthritis (RA) and whether levels are correlated with disease activity and other variables.Methods.Our study included 71 patients with RA and 50 age- and sex-matched healthy controls. Clinical characteristics and laboratory measures, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and 28-joint Disease Activity Score (DAS28) were assessed. Plasma levels of sTREM-1 and tumor necrosis factor-α (TNF-α) were measured by ELISA.Results.Patients with RA had significantly higher plasma sTREM-1 levels than healthy controls (170.10 ± 84.71 pg/ml vs 97.41 ± 40.64 pg/ml; p < 0.001). In patients with RA, plasma sTREM-1 levels were found to be correlated with DAS28, ESR, CRP, white blood cell counts, neutrophil counts, and plasma TNF-α levels (r = 0.329, p = 0.005; r = 0.241, p = 0.043; r = 0.314, p < 0.001; r = 0.261, p = 0.028; r = 0.278, p = 0.019; and r = 0.313, p = 0.009, respectively). Plasma sTREM-1 levels in patients with active disease status (DAS28 > 3.2) were significantly higher than in those with low disease status (DAS28 ≤ 3.2; 208.89 ± 100.14 pg/ml vs 150.29 ± 68.70 pg/ml; p = 0.005).Conclusion.Patients with RA had higher plasma sTREM-1 levels than healthy controls, and plasma sTREM-1 levels were correlated with disease activity measures, suggesting that plasma sTREM-1 could play a role in the inflammatory process associated with TNF-α, and that it may be a useful disease activity marker in RA.

Production and Expression of Inflammatory Mediators in Leukocytes of Sickle Cell Anaemia Patients and Effects of Hydroxyurea Therapy on This Production

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2490-2490
Author(s):  
Carolina Lanaro ◽  
Carla Fernanda Franco-Penteado ◽  
Dulcinéia M Albuquerque ◽  
Sara T.O. Saad ◽  
Nicola Conran ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell ◽  
Inflammatory Mediators ◽  
Healthy Controls ◽  
Gene Expressions ◽  
Tnf Α ◽  
Ifn Γ ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Hydroxyurea Therapy

Abstract Leukocytosis is frequently observed in sickle cell disease (SCD) in the absence of bacterial infection. An elevated baseline leukocyte count is associated with an increased risk of early death and leukocytes play a significant role in the initiation of vaso-occlusive events. Inflammation, cell adhesion to vascular endothelium, and subsequent endothelial injury appear to contribute to sickle cell anemia (SCA) vaso-occlusion. Furthermore, blood levels of inflammatory and anti-inflammatory cytokines are reported to be elevated (TNF-α, IL-6, IL-10, GM-CSF), both in steady state and during crisis, but reports have been conflicting and a conclusive role for these molecules in the disease remains to be established. Furthermore, the effect of hydroxyurea therapy (HU) on the release of inflammatory mediators is not understood. The aim of this study was to determine plasma levels and leukocyte gene expressions of inflammatory mediators in healthy controls (n=30), steady-state SCA patients (n=45) and SCA patients on HU therapy (n=24). qRT-PCR analysis was use to examine gene expression and ELISA protein production. TNF-α, IL-8 and PGE2 plasma levels were significantly higher in the plasma of steady-state SCA individuals, when compared to control individuals (2.95 ± 0.4 pg/ml; 16.5 ± 2.5 pg/ml; 5.7 ± 0.6 pg/ml; 128.3 ± 12.2 pg/ml vs 1.43 ± 0.2 pg/ml, 88.5 ± 5.9 pg/ml, P=0.006; P&lt;0.0001; P=0.012, respectively). HU therapy significantly reversed augmented TNF-α (1.6 ± 0.2 pg/ml, P=0.006) and, interestingly, increased plasma anti-inflammatory IL-10 (P&lt;0.05). IL-10, IFN-γ, COX-2 and iNOS gene expressions were unaltered in SCA mononuclear cells (MC), however gene expressions of TNF-α, IL-8 and the protective enzyme, heme oxygenase-1 (HO-1), were significantly higher compared to healthy controls (0.46 ± 0.01; 0.08 ± 0.02; 0.21 ± 0.05 vs 0.18 ± 0.04; 0.02 ± 0.005; 0.035 ± 0.008; respectively, P&lt;0.02). HU therapy was not associated with significantly altered SCA MC inflammatory gene expression, although COX-2 mRNA expression was decreased (0.11 ± 0.05; 0.37 ± 0.12, SCAHU and SCA, respectively; P&lt;0.05). In SCA neutrophils, gene expressions of IL-8, IFN-γ, iNOS and HO-1 were significantly higher compared to those of control subjects (0.32 ± 0.07; 0.69 ± 0.19; 0.19 ± 0.06; 0.33 ± 0.09, P=0.02, P=0.025, P&lt;0.05; P=0.027, respectively). Patients on HU therapy demonstrated lower iNOS and higher IL-10 neutrophil gene expressions compared to SCA not on HU therapy (0.038 ± 0.03; 0.72 ± 0.13, P&lt;0.05; P&lt;0.05, respectively). Taken together, data suggest that alterations in the gene expressions and productions of a number of pro-and anti-inflammatory mediators are present in SCA and knowledge of these pathways may be important for identifying novel drug targets for the disease.

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