Increased expression of pro-inflammatory cytokines and metalloproteinase-1 by TGF-β
1 in synovial fibroblasts from rheumatoid arthritis and normal individuals

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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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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