POS0380 HORMONES OF ADIPOSE TISSUE IN PATIENTS WITH RHEUMATOID ARTHRITIS WHO HAVE REDUCED BODY WEIGHT

Background:Overweight in patients with rheumatic diseases is a condition that prolongs chronic inflammation and promotes synthesis and secretion of pro-inflammatory factors by adipose tissue, such as classical cytokines, tumor necrosis factor-α (TNF-α), adipokines (leptin, adiponektin, resistin) and other newly identified proinflammatory factors (fetuin A, nesfatin, hemerin, lipokain, serum amyloid protein 3) [1,2,3,4].Objectives:We investigated the relationship the effect of weight loss over 5 kg on the clinical manifestations of arthritis and hormones of adipose tissue serum levels in patients with rheumatoid arthritis (RA).Methods:We observed 80 female patients with RA (EULAR/ARA 2010 criteria) ranged in age from 39 to 69 years (mean age 51,72 ± 5,83 years) and the control group (60 healthy persons) with no complaints of pain in the joints over a lifetime, and without clinical signs of RA. Fetuin A, nesfatin, hemerin, leptin, adiponektin, resistin, visfatin level in serum was determined by ELISA-test using a commercial test systems.Results:As overweight patients were recruited in the study, hypocaloric diet low in animal fats and physiotherapy has been recommended to all participants. The positive dynamics in body weight loss over 5kg within 3 months has been achieved by 34 patients (27,2%). In RA patients with weight loss, a significant decrease in the serum level of pro-inflammatory cytokines (fetuin A, nesfatin, hemerin, leptin, adiponektin, resistin, visfatin (p<0.01)) and an increase in the quality of life according to the EQ-5D-5L (p<0.001) index were observed. This fact is probably explained by the decreased activity of inflammatory process after RA therapy and weight reduction.Conclusion:Thus, as a result of our study patients with RA with weight loss of more than 5 kg had more obvious pain relief than patients with the original weight. These findings suggest that there is a possible role of tissue pro-inflammatory cytokines in the pathogenesis of rheumatoid arthritis. All patients with RA with a BMI over 25 kg / m 2 are recommended to lower their weight to decrease the mechanical stress on the joints, and also to reduce the severity of inflammation and metabolic disorders.References:[1]Akhverdyan, Y. et al. The nicotinamide-phosphoribosiltransferase as a marker of systemic inflammation under osteoarthrosis // Klin Lab Diagn. 2017; 62(10):606-610.[2]Kravtcov, V. et al. High level of adipokines and overweight as factors contributing to osteoarthritis progression // Osteoporosis International, 2019. V.30 (2). S. 408.[3]Papichev, E. V. et al. Parameters of mineral-bone metabolism and fetuin-А level in patients with rheumatoid arthritis // Osteoporosis International, 2019. V.30 (2), S.381.[4]Polyakova J. et al. Tissue cytokines and their role in the pathogenesis of rheumatic diseases // Annal.Rheum.Diseases, 2019. Т. 30 (2), № S.387.Disclosure of Interests:None declared

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FRI0443 CLINICAL CHARACTERISTICS AND RELATED FACTORS OF COMMON RHEUMATIC DISEASES COMPLICATED WITH TUBERCULOSIS INFECTION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3717 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 819.1-819

Author(s):

L. Long ◽

G. Tang ◽

Y. Han ◽

Q. Peng ◽

J. Liu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Weight Loss ◽

Risk Factor ◽

High Risk ◽

Rheumatic Diseases ◽

Clinical Characteristics ◽

Control Group ◽

Average Dose ◽

Systemic Lupus ◽

Infection Group

Background:Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and syndrome(SS) are common rheumatic diseases with high incidence. Patients with those rheumatic diseases are at high risk of tuberculosis (TB) infection. However, manifestations can be atypical and easily confused with those of rheumatic disease itself. For those patients, diagnosis is usually much more difficult and further make treatment delayed. Sometimes it may lead to mistreatment. Therefore, it is important to recognize the clinical characteristics of those patients.Objectives:To explore the clinical characteristics and high risk factors of common systemic rheumatism complicated with tuberculosis infection.Methods:A total of 3,906 cases of RA, SLE, and SS common systemic rheumatism diagnosed in the People’s Hospital of Sichuan Province from January 2007 to January 2017 were collected with carefully exclusion with other infectious diseases and neoplastic disease. One hundred and five patients with TB were included as infection group, including 42 cases of RA, 41 cases of SLE, and 22 cases of SS. In the control group, 84 patients with RA, 82 patients with SLE, and 44 patients with SS were randomly selected from the corresponding rheumatoid non-infected patients hospitalized during the same period.Results:Fever was the most common symptom among 42 cases of RA, 41 cases of SLE, and 22 cases of SS with TB, accounting for 83.3%, 92.7%, and 68.2%, respectively. Cough, weight loss or fatigue was less common. For 41 cases of SLE and 22 cases of SS with TB, the proportion of pulmonary was 46.3%, 59.01%, respectively.In TB infection group, 27 cases of RA, 21 cases of SLE, and 13 cases of SS with TB had two or more chest CT findings, accounting for 59%, 57%, 62%, respectively. Lesions located in the posterior or posterior segment which TB usually affected were 9 cases(33.3%),9cases(42.9%),6cases(27.2%),respectively.The daily average dose of hormones within 1 year in TB infection group was higher than that in the control group (P<0.05). For SLE patients, lower counts of CD4+TL were found in TB infection group (P<0.05), while no such differences were found in RA and SS group.Conclusion:Patients with RA who have TB infection are mainly pulmonary TB. For SLE and SS patients, the chance of pulmonary tuberculosis and extra-pulmonary tuberculosis is similar.Symptoms of RA, SLE, SS with TB, such as fever, cough, weight loss, fatigue, are similar with the primary disease or other infection. Chest imaging is diversity. It is difficult to diagnose.Daily average dose of hormone within one year may be a common risk factor for RA, SLE and SS patients with TB. Decreased CD4+TL may also be a risk factor for SLE patients with TB.References:[1]Cantini F, Nannini C, Niccoli L, et al. Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics[J]. Mediators of Inflammation, 2017, 2017(6):1-15.[2]Ruangnapa K, Dissaneewate P, Vachvanichsanong P. Tuberculosis in SLE patients: rare diagnosis, risky treatment.[J]. Clinical & Experimental Medicine, 2015, 15(3):429-432.[3]Manuela D F, Bruno L, Martina S, et al. Lung Infections in Systemic Rheumatic Disease: Focus on Opportunistic Infections[J]. International Journal of Molecular Sciences, 2017, 18(2):293-315.[4]Disseminated tuberculosis masquerading as a presentation of systemic lupus erythematosus.Li JC, Fong W, Wijaya L, Leung YY.Int J Rheum Dis. 2017 Oct 2. doi: 10.1111/1756-185X.13195.[5]Handa R, Upadhyaya S, Kapoor S, et al. Tuberculosis and biologics in rheumatology: India – A special situation[J]. International Journal of Rheumatic Diseases, 2017, 51(2):115.Disclosure of Interests:None declared

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AB0103 THE AMBIGUOUS ROLE OF TISSUE CYTOKINES IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1226 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1350.1-1351

Author(s):

O. Korolik ◽

В. Zavodovsky ◽

E. Papichev ◽

Y. Polyakova ◽

S. L ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

High Activity ◽

Inflammatory Cytokines ◽

Stage Iii ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Individuals ◽

Fetuin A ◽

High Level ◽

Extraarticular Manifestations ◽

Pro Inflammatory Cytokines

Background:Cytokines stimulate the inflammatory response in the synovial membrane with rheumatoid arthritis (RA), initiate apoptosis of chondrocytes, activation of osteoclasts. The progression of comorbid diseases is also associated with the influence of cytokines. At the same time, anti-inflammatory cytokines are produced in various tissues. Their role in the pathogenesis of RA and its complications is ambiguous.Adiponectin (A) and Fetuin A (FA) are classified as negative acute phase proteins. Their concentration decreases with an increase in the level of pro-inflammatory cytokines: TNF-α, IL-1 and IL-6. Molecules A and FA, regardless of various factors and from each other, have similar effects in relation to pro-inflammatory cytokines, lipid and carbohydrate metabolism.Visfatin (V) and Nesfatin-1 (N-1) are pro-inflammatory adipokines. B is produced by cells of the mononuclear phagocytic system and connective tissue. N-1 - is produced by the cells of the intermediate and medulla oblongata and by the cells of the gastric mucosa.Objectives:to study the correlation of B, H-1, A and FA with the severity of inflammation in RAMethods:60 patients with RA and 30 healthy individuals were examined. The level of cytokines was determined by an indirect enzyme-linked immunosorbent assay using commercial test systems (Bio Vendor, cat No. RD195023100, Bio Vendor Human Fetuin-A, RaiBiotech, cat No. EIA-VIS-1, RaiBiotech, cat No. EIA-NESF). All patients underwent a full examination. Diagnosed with 2010 EULAR / ACR recommendations.Results:A decreased level of A (less than 0.8 μg/ml) was detected in 15 patients (25%), F-A (less than 653.55 μg/ml) in 16 (27%), a high level of V (more than 39 ng/ml) - in 55 (91%), N-1 (more than 37.95 ng/ml) - in 36 (60%), which is significantly more often than in healthy individuals. No significant difference in the levels of determined adipokines was found depending on the gender and body weight of patients with RA. The level of cytokines in RA is associated with high activity according to DAS 28, positivity by Anti-CCP, extraarticular manifestations of RA. The greatest correlation with extraarticular manifestations is with cutaneous and cerebral vasculitis. The levels of FA and N-1 also correlated with more pronounced radiological changes (X-ray stage III). FA circulating inhibitor of ectopic calcification. N-1 level is positively correlated with systolic blood pressure.Conclusion:A low level of A and FA, a high level of V and N-1 is characteristic of RA with the presence of high activity and positivity in the RF and Anti-CCP. An increased level of B is determined by more than 90% of patients, which indicates its high pro-inflammatory activity. The level of F and N-1 is also associated with the degree of damage to bone tissue (stage III, a lot of erosion). A positive correlation of level V and N-1, negative A and FA with the severity of inflammation in RA confirms the involvement of these proteins in the pathogenesis. A high level of A and V increases the risk of developing cardiovascular diseases and their complications, the effect of N-1 and FA is being studied. The effect of cytokines on osteoclasts and osteoblasts in RA is ambiguousReferences:[1]Visfatin and Rheumatoid Arthritis: Pathogenetic Implications and Clinical Utility. Polyakova Y. Curr Rheumatol Rev.2019[2]Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Kvlividze T. Klinicheskaya Laboratornaya Diagnostika.2019; 64 (1):53-56 (in Russ)[3]Fetuin-A. Novel hepatokine in rheumatoid arthritis laboratory diagnostics. Papichev E. Klinicheskaya Laboratornaya Diagnostika.2018; 63 (12):756-760 (in Russ)Disclosure of Interests:None declared

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Lipolysis defect in white adipose tissue and rapid weight regain

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00542.2018 ◽

2019 ◽

Vol 317 (2) ◽

pp. E185-E193 ◽

Cited By ~ 1

Author(s):

Michal Kasher-Meron ◽

Dou Y. Youn ◽

Haihong Zong ◽

Jeffery E. Pessin

Keyword(s):

Weight Loss ◽

Body Weight ◽

Adipose Tissue ◽

Caloric Restriction ◽

White Adipose Tissue ◽

Weight Regain ◽

Serine Phosphorylation ◽

Lean Body Weight ◽

Control Group ◽

Short Period

Weight regain after weight loss is a well-described phenomenon in both humans and animal models of obesity. Reduced energy expenditure and increased caloric intake are considered the main drivers of weight regain. We hypothesized that adipose tissue with obesity memory (OM) has a tissue-autonomous lipolytic defect, allowing for increased efficiency of lipid storage. We utilized a mouse model of diet-induced obesity, which was subjected to 60% caloric restriction to achieve lean body weight, followed by a short period of high-fat diet (HFD) rechallenge. Age-matched lean mice fed HFD for the first time were used as the control group. Upon rechallenge with HFD, mice with OM had higher respiratory exchange ratios than lean mice with no OM despite comparable body weight, suggesting higher utilization of glucose over fatty acid oxidation. White adipose tissue explants with OM had comparable lipolytic response after caloric restriction; however, reduced functional lipolytic response to norepinephrine was noted as early as 5 days after rechallenge with HFD and was accompanied by reduction in hormone-sensitive lipase serine phosphorylation. The relative lipolytic defect was associated with increased expression of inflammatory genes and a decrease in adrenergic receptor genes, most notably Adrb3. Taken together, white adipose tissue of lean mice with OM shows increased sensitization to HFD compared with white adipose tissue with no OM, rendering it resistant to catecholamine-induced lipolysis. This relative lipolytic defect is tissue-autonomous and could play a role in the rapid weight regain observed after weight loss.

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Mechanism of Body Weight Reducing Effect of Oral Boric Acid Intake

International Journal of Endocrinology ◽

10.1155/2013/914651 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5 ◽

Cited By ~ 10

Author(s):

Erhan Aysan ◽

Fikrettin Sahin ◽

Dilek Telci ◽

Merve Erdem ◽

Mahmut Muslumanoglu ◽

...

Keyword(s):

Skeletal Muscle ◽

Weight Loss ◽

Body Weight ◽

Adipose Tissue ◽

Boric Acid ◽

Tap Water ◽

Acid Group ◽

Control Group ◽

Acid Intake ◽

Brown Adipose

Objective. The effect of oral boric acid intake on reducing body weight has been previously demonstrated although the mechanism has been unclear. This research study reveals the mechanism.Subjects. Twelve mice were used, in groups of six each in the control and study groups. For five days, control group mice drank standard tap water while during the same time period the study group mice drank tap water which contains 0.28 mg/250 mL boric acid. After a 5-day period, gene expression levels for uncoupling proteins (UCPs) in the white adipose tissue (WAT), brown adipose tissue (BAT), and skeletal muscle tissue (SMT) and total body weight changes were analyzed.Results. Real time PCR analysis revealed no significant change in UCP3 expressions, but UCP2 in WAT (: 0.0317), BAT (: 0.014), and SMT (: 0.0159) and UCP1 in BAT (: 0.026) were overexpressed in the boric acid group. In addition, mice in the boric acid group lost body weight (mean 28.1%) while mice in the control group experienced no weight loss but a slight weight gain (mean 0.09%, ).Conclusion. Oral boric acid intake causes overexpression of thermogenic proteins in the adipose and skeletal muscle tissues. Increasing thermogenesis through UCP protein pathway results in the accelerated lipolysis and body weight loss.

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Leukemia Cells Resident in Adipose Tissue Display a Pro-Inflammatory Phenotype and Induce Lipolysis and Atrophy of Adipose Tissue

Blood ◽

10.1182/blood.v126.23.2765.2765 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2765-2765

Author(s):

Haobin Ye ◽

Nabilah Khan ◽

Marlene Balys ◽

John M. Ashton ◽

Biniam Adane ◽

...

Keyword(s):

Gene Expression ◽

Body Weight ◽

Adipose Tissue ◽

Fatty Acid ◽

Inflammatory Cytokines ◽

Leukemia Cells ◽

Paracrine Signaling ◽

Cytokines And Chemokines ◽

A Genome ◽

Pro Inflammatory Cytokines

Abstract Aberrant function of adipose tissue (AT) is seen in several diseases including cancer. Studies show that AT facilitates the progression of tumors through paracrine signaling of adipokines as well as regulation of cancer cell metabolism. However, the mechanism by which cancer cells corrupt the normal function of AT to gain proliferative and survival advantages is unknown. Using a murine model of blast crisis CML, we have shown enrichment of phenotypically primitive leukemia cells (Sca+/lin- leukemia cells, termed "PLCs") in the gonadal AT (GAT) as well as a fatty acid oxidation (FAO) regulatory role of AT. In this study, we evaluated the functional alteration of GAT in leukemic mice. We hypothesized that resident leukemia cells change the characteristics of GAT to obtain metabolic benefits. To test this hypothesis, we first examined whether PLCs in GAT differed from PLCs in other tissues including bone marrow, spleen and peripheral blood. To this end, we utilized RNA-seq to obtain a genome-wide transcriptional profile of PLCs in different tissues. We found PLCs in GAT had a distinct gene expression pattern with enrichment of inflammatory response genes. Specifically, pro-inflammatory cytokines and chemokines were highly expressed by PLCs in GAT (Figure 1). Furthermore, the expression of those genes was also increased in the stromal vascular fraction (SVF) of GAT, indicating resident leukemia cells induced inflammation in GAT. Collectively, these results suggest that leukemia cells found in GAT are distinct from leukemia cells in other tissues and may alter the function of GAT. Another characteristic observed in our model was atrophy of GAT (Figure 2) as well as loss of body weight during leukemia progression, indicating the presence of cancer cachexia. Loss of GAT was also found prior to loss of body weight, suggesting the presence of a pre-cachexia stage. We speculated that atrophy of GAT was due to lipolysis induced by inflammation. Indeed, leukemic GAT released more free fatty acid (FFA) and had a lipolytic pattern of adipokines compared to normal GAT. Elevated FFA and lipolytic adipokines were also detected in leukemic serum. Together, these observations demonstrate that GAT in leukemic mice is lipolytic. To gain insights into mechanisms involved in lipolysis of leukemic GAT, we examined expression of lipolysis-related genes (Figure 3). We found that leukemic GAT had increased expression of the adipose triglyceride lipase (Atgl), which is a rate-limiting lipase controlling lipolysis, and reduced expression of lipoprotein lipase (Lpl), whose expression correlates with the influx of fatty acids into adipocytes. Additionally, decreased expression of the cell death activator CIDE-A (Cidea), which is a lipid droplet (LD) associated protein that shields LDs from lipases and inhibits lipolysis, was found in leukemic GAT. Together, these findings suggest that regulation of lipid metabolism is disrupted in leukemic GAT, leading to lipolysis. To test whether resident leukemia cells contribute to the atrophy of GAT, we examined the lipolytic effect of the pro-inflammatory cytokines and chemokines that were highly expressed by PLCs in GAT. We found that IL-1β and CSF2 induced lipolysis and engendered similar gene expression patterns of lipolysis-related genes in 3T3-L1 adipocytes. Notably, palmitate induced the expression of IL-1β in leukemia cells while it had an opposite effect in naive hematopoietic cells, implying a positive feedback loop where inflammation induces lipolysis which induces IL-1β which in turn augments inflammation. Additionally, an increased amount of IL-1β was observed in leukemic serum. Taken together, these data suggest that resident leukemia cells contribute to the atrophy of GAT through paracrine signaling of pro-inflammatory agents. This phenomenon appears to benefit leukemia cells by fostering FAO and metabolic properties that enhance leukemia cell survival. Thus, targeting pathways that mediate inflammation and/or lipolysis may create a microenvironment that is less favorable to leukemia cells. Disclosures No relevant conflicts of interest to declare.

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AB0097 TISSUE CYTOKINES AS NEW DIAGNOSTIC BIOMARKER OF BONE METABOLISM DISORDERS IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6711 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1348.2-1348

Author(s):

V. Kravtsov ◽

L. Arefeva ◽

S. L

Keyword(s):

Rheumatoid Arthritis ◽

Bone Mineral Density ◽

Bone Density ◽

Inflammatory Cytokines ◽

Bone Mineral ◽

Serum Adiponectin ◽

Mineral Density ◽

Fetuin A ◽

Normal Bone ◽

Pro Inflammatory Cytokines

Background:Bone mineral density and proteins/peptides determination in blood and urine as markers of bone resorption and formation are currently used to diagnose osteoporosis (OP) and metabolic bone diseases. Recent evidence suggests that in RA changes in the secretion of hormones of white adipose tissue can be revealed [1,2,3,4].Objectives:To study the clinical and diagnostic value of serum fetuin A, nesfatin, hemerin, leptin, adiponektin, resistin, visfatin determination in RA patients complicated by OP.Methods:We examined 88 women with documented diagnosis of RA and mean disease duration of 6.56±0.88 years. We used EULAR/ARA 2010 criteria to diagnose the patients. Female patients with II degree of disease activity (DAS28), Steinbrocker stage II (erosive), rheumatoid factor- and anti-cyclic-citrullinated peptide antibody-positive were prevalent. We excluded patients who had surgery or developed an infection within the last 8 weeks, pregnant and breast-feeding women, those with severe heart, liver or kidney disease, immune deficiency, leukopenia or chronic infection.A control group of 45 healthy females aged of 25 and 59 years were included in the study. There were no reported findings of joint pain and RA symptoms in the group. The groups were adjusted for age (p>0.05) and showed no statistically significant differences.We measured serum fetuin A, nesfatin, hemerin, leptin, adiponektin, resistin, visfatin levels (µg/ml) using ELISA commercial test systems. We used spectrophotometer with wavelength of 450 nm to detect the test results («Multiskan» immunoenzyme analyzer, Finland). We plotted a curve using computer software. We diagnosed OP using dual-energy X-ray absorptiometry with LUNAR DPX PRO (GE, USA).Results:At the first stage, the level of pro-inflammatory cytokines was studied in a group of healthy individuals. Then, the reference values of these indicators were measured as М ± 2δ. Patients with OP and RA had significantly higher levels of serum pro-inflammatory cytokines (р<0.001). For example, mean serum Adiponectin levels in RA patients who had normal bone density and had no OP were 35.21±0.6 µg/ml. Mean serum Adiponectin levels in RA/OP patients with low bone mineral density were 52.42±0.69 µg/ml. Adiponectin levels of 44 µg/ml and higher were associated with osteoporosis. Adiponectin levels of 43.9 µg/ml and lower were associated with normal bone density. Other pro-inflammatory cytokines have demonstrated similar dynamics of level serum.Conclusion:Thus, we revealed that fetuin A, nesfatin, hemerin, leptin, adiponektin, resistin, visfatin levels depend on osteoporosis presence in RA patients. The test may be used to reduce the risk of low-energy fractures and to improve the quality of life in RA.References:[1]Akhverdyan Y. et al. Laboratory markers of inflammation and serum nicotinamide phosphoribosyltransferase level in rheumatoid arthritis patients // Ann. Rheum. Dis., 2017, vol.76, suppl.2, p.1149.[2]Kvlividze Z. et al. Elevated nesfatin-1 levels in patients with rheumatoid arthritis // Ann Rheum Dis, 2018, vol.77, p.A1762.[3]Papichev E. et al. Fetuin-A: clinical and laboratory associations in women with rheumatoid arthritis // Ann Rheum Dis, 2018, vol.77, p.A1228.[4]Polyakova J. S. et al. Serum visfatin determination in rheumatoid arthritis // Ann. Rheum. Dis. 2014; 73 (Suppl2).Disclosure of Interests:None declared

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AB0827 SERUM NESPHATIN-1 IN PATHOGENESIS RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2503 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1437.2-1438

Author(s):

T. Kvlividze ◽

V. Polyakov ◽

В. Zavodovsky ◽

Y. Polyakova ◽

L. Seewordova ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Blood Serum ◽

Inflammatory Cytokines ◽

Inflammatory Markers ◽

Healthy People ◽

Healthy Individuals ◽

Markers Of Inflammation ◽

High Level ◽

Pro Inflammatory Cytokines

Background:Interest in highly specialized tissue cytokines contributed to the discovery of new biologically active molecules. Nesfatin-1 (NF) - discovered in 2006 as an anorexigenic factor. NF-1 is believed to be involved in the regulation of energy homeostasis by regulating appetite and water intake. The role of NF-1 in the pathogenesis of inflammatory diseases is poorly understood. Recently, studies have found a relationship between an increased level of NF-1 and inflammatory markers in various pathologies.Objectives:Study of the level of nesfatin-1 in the blood serum of healthy people, determination of the correlation between the level of NF-1 with the severity of clinical symptoms and classic markers of inflammation in patients with RA.Methods:120 persons were examined: 90 patients with RA and 30 healthy people. All patients underwent a complete clinical and laboratory examination. Plasma NF-1 levels were determined using commercial test systems (RaiBiotech, cat # EIA-NESF) according to the manufacturer’s instructions. Patients with various forms of RA were comparable in age to the group of healthy individuals. Statistical processing of clinical examination data was carried out using the “STATISTICA 10.0 for Windows” software package. Quantitative data were processed statistically using the parametric Student’s t-test, qualitative data using the non-parametric chi-square test. The significance of differences between groups was determined using analysis of variance. The results were considered statistically significant at p <0.05.Results:The average level of NF-1 in blood serum in healthy individuals was 31.79 ± 3.21 ng / ml (M ± σ). The level of normal NF-1 values in healthy individuals, defined as M ± 2σ, ranged from 25.3 to 37.83 ng / ml. There was no significant difference in the levels of circulating NF-1 and BMI in healthy individuals and patients with RA (p> 0.05). The inverse relationship of a lower level of NF-1 with an increase in BMI was not significant.Group 1 (66 patients with RA) with increased serum NF-1 levels (> 37.83 ng / ml), and group 2 (44 patients) with normal values (<37.83 ng / ml). A high level of NF-1 was characteristic for patients with high activity according to DAS28, RF seropositive, ACCP-positive, with extra-articular manifestations, who had been ill for 10 years or more. A reliable relationship between the level of NF-1 in the blood serum and laboratory parameters of RA activity - ESR, CRP, was shown, and secondary synovitis was more common. Our data show a direct correlation between the NF-1 level of the pro-inflammatory markers of RA.Conclusion:The positive correlation between the level of NF-1 and classical markers of inflammation, such as CRP and ESR, confirms the involvement of NF-1 in the pathophysiology of inflammation in RA. This is also evidenced by the correlation of a high level of NF-1 in the blood serum with a more severe clinical picture of RA. It is known that NF-1 can promote the release of pro-inflammatory cytokines such as interleukin-8 (IL-8), interleukin-6 (IL-6), and macrophage inflammatory protein-1a (MIP-1a) in the chondrocytes of RA patients.It is necessary to further study the role of NF-1 in the pathogenesis of systemic inflammatory reactions and the possibility of targeting pro-inflammatory cytokines, the possibility of regulating the level of NF-1 by drugs.References:[1]Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R. Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R., Polyakova Yu.V., Sivordova L.E., Yakovlev A.T., Zborovskaya I.A. Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Klinicheskaya Laboratornaya Diagnostika (Russian Clinical Laboratory Diagnostics). 2019; 64 (1): 53-56 (in Russ.).Disclosure of Interests:None declared

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AB0167 PECULIARITIES OF INTERACTION OF CHRONIC INFLAMMATION AND DEPRESSION IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3087 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1110.1-1110

Author(s):

A. Aleksandrov ◽

N. Aleksandrova

Keyword(s):

Rheumatoid Arthritis ◽

Vitamin D ◽

Inflammatory Cytokines ◽

Depressive Disorders ◽

Severe Depression ◽

Mild Depression ◽

Group Iii ◽

Group I ◽

Severity Of Depression ◽

Pro Inflammatory Cytokines

Background:In patients with rheumatoid arthritis (RA), a high prevalence of depression and anxiety is observed, and the severity of these conditions depends on the degree of vitamin D deficiency. The role of the main mediator, with the help of which psychological and physical stress factors can contribute to the development of depression and systemic diseases, has been attributed to inflammation in recent years.Objectives:to assess the dependence of depressive disorders on vitamin D deficiency and the level of pro-inflammatory cytokines in patients with RA.Methods:88 women with a reliable diagnosis of RA (mean age 54.2 ± 12.0 years old, disease duration 9.0 [3.5; 16.0] years) were under observation. Beck’s depression inventory (BDI-II) was used to assess the presence of depressive symptoms. ELISA test was used to measure serum cytokines (IL-1, IL-6) and serum 25(OH)D levels.Results:The presence of depression was found in 66% of patients with RA. An insufficient level of 25(OH)D (<30 ng / ml) was determined in 89.8% of cases. In RA patients with no signs of depression, the level of 25(OH)D showed maximum values and significantly differed from that in the groups of patients with moderate (p = 0.028) and severe depression (p <0.001). A negative correlation (r = -0.38, n = 88, p <0.05) was established between the level of 25(OH)D and the severity of depression. A positive relationship was also found between 25(OH)D and ESR (r = 0.29, n = 73, p <0.05) and a negative relationship with the number of painful joints (r = -0.29, n = 76, p <0.05). Probably, vitamin D is indirectly involved in inflammatory processes in joints and in central sensitization, which provokes chronic pain and psychological disorders in patients with RA.The level of IL-6 in patients with RA with moderate and severe depression (n=18; 14.6 ± 6.7 pg/ml) significantly exceeded the parameters of patients with RA without depressive disorders (n=30; 9.8 ± 3.7; p = 0.003). There was also a tendency to increase IL-6 in the group of patients with moderate and severe depression compared with patients with mild depression (p = 0.06). IL-1β values significantly increased with the progression of depression (without depression – mild depression, p = 0.034; mild – moderate, p <0.001; moderate – severe depression, p = 0.044). A positive correlation of average severity was revealed between the degree of depression (according to BDI-II) and the dose of glucocorticoids (GC) at the time of the study (r = 0.33, p = 0.002). An increase in the GC dose in the short term can aggravate depressive disorders in RA patients (Table 1).Table 1.Indicators of levels of depression and IL-1β depending on the dose of GCGroup I (n=26), without GCGroup II (n=45),GC <10 mg / dayGroup III (n=17),GC ≥10 mg / dayDepression level according to BDI-II, points (Me [P25; P75])8,5[5;16]14[9;17]19[14;29] *III-IIL-1β level, pg / ml (M ± SD)4,57 ± 1,83*I-II6,04 ± 3,276,52 ± 5,16* - intergroup differences are reliable, p <0.05Patients who used GC in a daily dose of ≥10 mg / day (group III) had a higher degree of depression compared to patients with RA from group I (z = -2.98; p = 0.003). In patients with RA in the first group, the level of IL-1β was significantly higher (pI-II = 0.039) than in patients with GC prescription in minimal doses (up to 10 mg / day) (Table 1). Glucocorticoid hormones suppress pro-inflammatory cytokines. As a rule, this effect is not observed in patients with depression. This fact may indicate a violation of homeostatic mechanisms. IL-1β is thought to be the first step in the pro-inflammatory response to psychological stress and is capable of inducing a subsequent cascade of other inflammatory cytokine responses.Conclusion:Restoring the normal level of 25(OH)D in the blood serum of patients with RA can positively affect psychological indicators by reducing the severity of depression and manifestations of pain. The activation of pro-inflammatory cytokines during stress and depression suggests that suppression of the inflammatory response can also reduce the symptoms of depression in RA patients.Disclosure of Interests:None declared

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Human umbilical cord mesenchymal stem cell-derived extracellular vesicles attenuate experimental autoimmune encephalomyelitis via regulating pro and anti-inflammatory cytokines

Scientific Reports ◽

10.1038/s41598-021-91291-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Samira Ahmadvand Koohsari ◽

Abdorrahim Absalan ◽

Davood Azadi

Keyword(s):

Spinal Cord ◽

Body Weight ◽

Extracellular Vesicles ◽

Inflammatory Cytokines ◽

Clinical Score ◽

Human Umbilical Cord ◽

Therapeutic Effects ◽

Leukocyte Infiltration ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

AbstractThe therapeutic effects of mesenchymal stem cells-extracellular vesicles have been proved in many inflammatory animal models. In the current study, we aimed to investigate the effect of extracellular vesicles (EVs) derived from human umbilical cord-MSC (hUCSC-EV) on the clinical score and inflammatory/anti-inflammatory cytokines on the EAE mouse model. After induction of EAE in C57Bl/6 mice, they were treated intravenously with hUCSC-EV or vehicle. The clinical score and body weight of all mice was registered every day. On day 30, mice were sacrificed and splenocytes were isolated for cytokine assay by ELISA. Cytokine expression of pro-/anti-inflammatory cytokine by real-time PCR, leukocyte infiltration by hematoxylin and eosin (H&E) staining, and the percent of glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) positive cells by immunohistochemistry were assessed in the spinal cord. Our results showed that hUCSC-EV-treated mice have lower maximum mean clinical score (MMCS), pro-inflammatory cytokines, and inflammatory score in comparison to the control mice. We also showed that hUCSC-EV administration significantly improved body weight and increased the anti-inflammatory cytokines and the frequency of Treg cells in the spleen. There was no significant difference in the percent of GFAP and MBP positive cells in the spinal cord of experimental groups. Finally, we suggest that intravenous administration of hUCSC-EV alleviate induce-EAE by reducing the pro-inflammatory cytokines, such as IL-17a, TNF-α, and IFN-γ, and increasing the anti-inflammatory cytokines, IL-4 and IL-10, and also decrease the leukocyte infiltration in a model of MS. It seems that EVs from hUC-MSCs have the same therapeutic effects similar to EVs from other sources of MSCs, such as adipose or bone marrow MSCs.

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Brown adipose tissue activation in a rat model of Parkinson’s disease

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00049.2017 ◽

2017 ◽

Vol 313 (6) ◽

pp. E731-E736 ◽

Cited By ~ 5

Author(s):

Wenjuan Wang ◽

Xiangzhi Meng ◽

Chun Yang ◽

Dongliang Fang ◽

Xuemeng Wang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Weight Loss ◽

Body Weight ◽

Adipose Tissue ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

Energy Intake ◽

Rat Model ◽

Sympathetic Denervation ◽

Brown Adipose

Loss of body weight and fat mass is one of the nonmotor symptoms of Parkinson’s disease (PD). Weight loss is due primarily to reduced energy intake and increased energy expenditure. Whereas inadequate energy intake in PD patients is caused mainly by appetite loss and impaired gastrointestinal absorption, the underlying mechanisms for increased energy expenditure remain largely unknown. Brown adipose tissue (BAT), a key thermogenic tissue in humans and other mammals, plays an important role in thermoregulation and energy metabolism; however, it has not been tested whether BAT is involved in the negative energy balance in PD. Here, using the 6-hydroxydopamine (6-OHDA) rat model of PD, we found that the activity of sympathetic nerve (SN), the expression of Ucp1 in BAT, and thermogenesis were increased in PD rats. BAT sympathetic denervation blocked sympathetic activity and decreased UCP1 expression in BAT and attenuated the loss of body weight in PD rats. Interestingly, sympathetic denervation of BAT was associated with decreased sympathetic tone and lipolysis in retroperitoneal and epididymal white adipose tissue. Our data suggeste that BAT-mediated thermogenesis may contribute to weight loss in PD.

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