High humidity aggravates the severity of arthritis in collagen-induced arthritis mice by upregulating xylitol and L-pyroglutamic acid

Abstract Background Humidity was an unfavorable factor for patients with rheumatoid arthritis (RA). RA disease activity was severe in high humidity conditions. However, there is no evidence to demonstrate the effects of humidity on arthritis in the animal experiments and explore its relevant mechanism. Methods Using the DBA/1 mice, this study addressed the effects of a high humidity (80 ± 5%) on arthritis in collagen-induced arthritis (CIA) mice. Then, this study used the gas chromatography-mass spectrometer (GC-MS) to explore alterations in serum metabolome caused by the high humidity. Furthermore, xylitol and L-pyroglutamic acid, which were both significantly upregulated by the high humidity, were selected to further study their effects on arthritis in the CIA mice. Results The high humidity (80 ± 5%) could aggravate arthritis variables including increasing arthritis score and swelling, serum autoantibodies (anti-COII and anti-CCP), and proinflammatory cytokines (IL-6, IL-17A, and G-CSF). In addition, the high humidity could cause significant alterations in serum metabolome in the CIA mice. Xylitol and L-pyroglutamic acid were the representative serum metabolites that were significantly upregulated by the high humidity. Further experiments demonstrated that the supplementation of 0.4 mg/mL xylitol in drinking water after inducing the CIA model and 2.0 mg/mL in drinking water before inducing the CIA model could both aggravate arthritis in the CIA mice. Conclusions These data demonstrated that high humidity was not beneficial for arthritis development and its mechanism might be associated with xylitol and L-pyroglutamic acid.

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Total Flavonoids of Bidens pilosa Ameliorates Bone Destruction in Collagen-Induced Arthritis

Planta Medica ◽

10.1055/a-1352-5124 ◽

2021 ◽

Author(s):

Mengqin Hong ◽

Xingyu Fan ◽

Shengxiang Liang ◽

Wang Xiang ◽

Liting Chen ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Proinflammatory Cytokines ◽

Bone Destruction ◽

Nuclear Factor Κb ◽

Total Flavonoids ◽

Nuclear Factor ◽

Collagen Induced Arthritis ◽

Bidens Pilosa ◽

X Ray ◽

Receptor Activator

AbstractRheumatoid arthritis is a chronic autoimmune disease characterized by the infiltration of synovial inflammatory cells and progressive joint destruction. Total flavonoids of Bidens pilosa have been used against inflammation in rheumatoid arthritis, but its role in bone destruction remains to be explored. The aim of this paper was to study whether total flavonoids of B. pilosa relieve the severity of collagen-induced arthritis in rats, particularly whether it regulates the production of proinflammatory cytokines and the receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand/osteoprotegerin signaling pathway. In this research, a collagen-induced disease model was induced in adult rats by subcutaneous injection of collagen II. Total flavonoids of B. pilosa at different doses (40, 80, and 160 mg/kg/d) were administered intragastrically, while methotrexate (1 mg/kg/w) was injected intraperitoneally as a positive control. Paw swelling, arthritis score, and body weight were assessed and evaluated. The severity of joint damage was determined using X-ray and confirmed by histopathology. The expression levels of receptor activator of nuclear factor-κB ligand, osteoprotegerin, IL-1β, IL-17, and TNF in the serum and tissue were assayed using ELISA and immunohistochemistry. We found that total flavonoids of B. pilosa attenuated collagen-induced arthritis at the macroscopic level, and total flavonoids of B. pilosa-treated rats showed reduced paw swelling, arthritis scores, and X-ray appearance of collagen-induced arthritis in addition to improved histopathological results. These findings were consistent with reduced serum and tissue receptor activator of nuclear factor-κB ligand, TNF, IL-1β, and IL-17 levels but increased osteoprotegerin levels. Our data suggest that total flavonoids of B. pilosa attenuate collagen-induced arthritis by suppressing the receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin pathway and the subsequent production of proinflammatory cytokines. In addition, total flavonoids of B. pilosa may be a promising therapeutic candidate for the management of rheumatoid arthritis.

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AB0256 INCREASED SERUM PROCALCITONIN CONCENTRATION IN PATIENTS WITH RHEUMATOID ARTHRITIS FREE OF ACTIVE INFECTION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.172 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1427.1-1427

Author(s):

K. J. Ng ◽

K. Y. Huang ◽

C. H. Tung ◽

M. C. Lu ◽

N. S. Lai

Keyword(s):

Rheumatoid Arthritis ◽

Bacterial Infection ◽

Disease Activity ◽

Proinflammatory Cytokines ◽

Linear Regression Analysis ◽

Manuscript Preparation ◽

Biologic Agent ◽

Healthy Controls ◽

Active Infection ◽

Age And Sex

Background:Rheumatoid arthritis (RA) is the most common inflammatory arthritis, affecting 0.5-1% of the general population worldwide. Patients with RA are often in a relatively immunocompromised status. Previous study have evaluated procalcitonin (PCT) application among autoimmune and autoinflammatory diseases for the diagnosis of systemic bacterial infection (1, 2) To date, the correlation of baseline PCT levels and RA disease activities, different treatment, or the expression of proinflammatory cytokines in patients with RA remained unknown.Objectives:To investigate the baseline PCT levels among patients with RA without active infection compared with healthy controls and to understand the relationship of PCT with RA disease activity, treatment received by patients, and the expression of proinflammatory cytokines.Methods:Patients aged 20 years and above, with clinician-confirmed diagnosis of RA were included during regular outpatient visits. RA disease activity was measured using the DAS28-ESR.Results:A total of 623 patients with RA and 40 healthy subjects were recruited in this study. The mean PCT were significantly higher in patients with RA (6.90 ± 11.81 * 10-3ng/mL) compared with healthy controls (1.14 ± 3.26 * 10-3ng/mL) (p = 0.002). After adjusted for age and sex, the PCT levels remain significantly elevated in patients with RA (p = 0.001). PCT was not significantly correlated with biologic agent, age, sex, disease duration, disease activity, C-reactive protein, conventional synthetic disease-modifying antirheumatic drugs (csDMARD), and comorbidities. Multiple linear regression analysis showed that PCT was inversely associated with the expression of IL-1β (B = −0.883; CI 95% −1.388, −0.378, p = 0.001) and IFN-α (B = −1.197; CI 95% −2.153, −0.242, p = 0.014) after adjusted for age and sex.Conclusion:Patients with RA have significantly higher baseline PCT compared with healthy controls. The treatment received by patients with RA did not affect the level of PCT. Further investigation is required to determine the optimal cutoff value of PCT among patients with RA before applying it in daily clinical practice.References:[1]Scire CA, Cavagna L, Perotti C, Bruschi E, Caporali R, Montecucco C. Diagnostic value of procalcitonin measurement in febrile patients with systemic autoimmune diseases. Clin Exp Rheumatol. 2006;24(2):123−8.[2]Delevaux I, Andre M, Colombier M, Albuisson E, Meylheuc F, Begue RJ, et al. Can procalcitonin measurement help in differentiating between bacterial infection and other kinds of inflammatory processes? Ann Rheum Dis. 2003;62(4):337−40.Acknowledgments:The authors gratefully acknowledge Dr. Malcolm Koo for advice on statistical analysis and manuscript preparation.Disclosure of Interests:None declared

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A Natural Flavonoid Glucoside, Icariin, Regulates Th17 and Alleviates Rheumatoid Arthritis in a Murine Model

Mediators of Inflammation ◽

10.1155/2014/392062 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 14

Author(s):

Liqun Chi ◽

Wenyuan Gao ◽

Xiangrong Shu ◽

Xin Lu

Keyword(s):

Rheumatoid Arthritis ◽

Th17 Cells ◽

Cathepsin K ◽

Serum Levels ◽

Arthritis Score ◽

Collagen Induced Arthritis ◽

Pharmacological Activities ◽

Bone Degradation ◽

Autoimmune Inflammatory Disease

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that causes deformity of the joints and physical disability. Icariin, a natural flavonoid glucoside isolated from plants in theEpimediumfamily, has been proven to have various pharmacological activities. A recent study showed that icariin suppressed cartilage and bone degradation in mice of collagen-induced arthritis. However, the mechanism needs to be further investigated. In our current study, we found that icariin reduced the arthritis score and the incidence of arthritis compared with that in mice treated with water. Icariin inhibits the expression of various osteoclastogenic markers, such asβ3 integrin, cathepsin K, and MMP9in vitro. Icariin treatment in mice with CIA also resulted in less number of Th17 cells and decreased ratio of CD4+IL-17+cells. The alleviated arthritis score and incidence of arthritis and reduced serum levels of IgG2a induced by icariin were abolished with additional IL-17 administration. Furthermore, icariin inhibited STAT3 activation in T cells and STAT3 inhibitor resulted in decreased IL-17 production and alleviated RA. In conclusion, icariin decreases Th17 cells and suppresses the production of IL-17, which contributes to the alleviated rheumatoid arthritis, through the inhibition of STAT3 activation.

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YKL-40 and cytokines - a New Diagnostic Constellation in Rheumatoid Arthritis?

Folia Medica ◽

10.1515/folmed-2017-0013 ◽

2017 ◽

Vol 59 (1) ◽

pp. 37-42 ◽

Cited By ~ 9

Author(s):

Maria H. Kazakova ◽

Anastas Z. Batalov ◽

Nonka G. Mateva ◽

Zlatimir G. Kolarov ◽

Victoria S. Sarafian

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Disease Activity ◽

Cancer Cells ◽

Proinflammatory Cytokines ◽

Dominant Role ◽

Strong Association ◽

Study Finding ◽

Activated Macrophages ◽

Tnf Α

Abstract Background: Rheumatoid arthritis (RA) causes chronic inflammation and alteration of articular tissue and joints. The pathogenesis of the disease remains unclear although it is known that proinflammatory cytokines play a major role in its induction. YKL-40 is a chitinase-like glycoprotein produced by activated macrophages, neutrophils, arthritic chondrocytes and cancer cells. It has been shown that YKL-40 is implicated in tissue remodeling, angiogenesis and inflammation. Aim: to investigate serum and synovial YKL-40 levels in relation to IL-1β, TNF-α, and IL-6 in RA patients. Materials and methods: Serum and synovial concentrations of YKL-40, TNF-α, IL- 6, and IL-1β were determined by ELISA in 39 patients (mean age 53.18 ± 16.54 yrs) with active RA. Results: Serum YKL-40 levels were increased in all patients. The highest levels were found in synovial fluid (P<0.01). Our study showed a strong association between serum and synovial levels of YKL-40 and serum TNF-α and IL-1 β (P<0.05). Conclusion: This is the first study finding a significant correlation between serum TNF-α and IL-1β and YKL-40 in active RA. We suggest that these molecules together might play a dominant role in the pathogenesis and disease activity and could possibly serve as a new diagnostic constellation in rheumatoid arthritis.

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SAT0021 STRUCTURAL EFFECTS OF LOCAL CRYOTHERAPY IN RHEUMATOID ARTHRITIS: A STUDY IN ADJUVANT-INDUCED ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4118 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 940.2-941

Author(s):

C. Peyronnel ◽

V. Petitcolin ◽

P. Totoson ◽

H. Martin ◽

F. Verhoeven ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Skin Temperature ◽

Cold Spray ◽

Radiographic Progression ◽

Joint Destruction ◽

Arthritis Score ◽

Adjuvant Induced Arthritis ◽

Radiological Score ◽

Local Cryotherapy

Background:The control of joint destruction caused by rheumatoid arthritis (RA) is a key issue in the treatment of this disease. Recent evidence showed that radiographic progression of joint damage occur despite a sharp decrease in disease activity and the use of aggressive Disease Modifying Anti-Rheumatic Drug (DMARD) therapies [1]. Whether alternative treatments such as cryotherapy may have beneficial effects on joint destruction at the early stages of the disease remains to be demonstrated, but such strategy would be of interest as it would not interfere with DMARDs treatment.Objectives:The aim of this study was to evaluate the effect of a 14-days-treatment of local cryotherapy on radiological outcomes in rat adjuvant induced arthritis.Methods:Adjuvant-induced arthritis (AIA) was induced in 6-weeks old male Lewis rats by injection ofMycobacterium butyricumin Freund’s incomplete adjuvant at the basis of the tail. A control group received saline. At the onset of arthritis, AIA rats were treated or not by application of cryotherapy on paws using either a cold spray or ice, twice a day for 14 days. Arthritis score and paws skin temperature was daily monitored. At the end of treatment, radiological exam of hind paws was performed and a score taking into account (swelling, osteoporosis, cartilage destruction, bone erosion, bone destruction and new bone formation) was assigned, according to Ackermanet al[2]. Circulating levels of cytokines (IL-6, IL-1β, TNF-α) was measured by Magpix Luminex kit.Results:Compared to untreated AIA, local cryotherapy significantly reduced the progression of arthritis score, whatever the modality (p<0.05), and to the same extent (reduction of arthritis score at day 24 post-immunization: -38% with cold spray, p<0.01, -37% with ice, p<0.01). Radiological score was significantly reduced by both treatments with no difference between the two treatments (-33% with cold spray, p<0.01, -44% with ice, p<0.01). All the items of the radiological score were equally reduced by ice and cold spray except swelling that was significantly reduced only by ice. Interestingly, the use of the cold spray induced a greater decrease in the skin temperature than the ice treatment (18.32 ± 0.07 °C vs 20.46 ± 0.08 °C, p<0.001). Conversely, cryotherapy did not significantly change the level of cytokines. No correlation was found between radiological score and arthritis score or cytokine levels.Conclusion:These data demonstrated that local cryotherapy had positive effects on structural damage in adjuvant-induced arthritis. The mechanisms involved remain now to be determined. These results suggest that local cryotherapy would be an interesting complement to conventional DMARDs in early RA.References:[1] Ten Klooster, P. M.et al.Radiographic progression can still occur in individual patients with low or moderate disease activity in the current treat-to-target paradigm: real-world data from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry.Arthritis Res. Ther.21, 237 (2019).[2] Ackerman, N. R.et al.Effects of naproxen on connective tissue changes in the adjuvant arthritic rat.Arthritis Rheum.22, 1365–1374 (1979).Disclosure of Interests:Célian Peyronnel: None declared, Valentin Petitcolin: None declared, Perle Totoson: None declared, Hélène Martin: None declared, Frank Verhoeven: None declared, Céline Demougeot Grant/research support from: With an institutional support from Pfizer.

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Nitric Oxide: Link between Inflammation and Endothelial Dysfunction in Rheumatoid Arthritis

International Journal of Angiology ◽

10.1055/s-0036-1597577 ◽

2016 ◽

Vol 26 (03) ◽

pp. 165-169 ◽

Cited By ~ 6

Author(s):

Nidhi Garg ◽

Ashit Syngle ◽

Pawan Krishan

Keyword(s):

Rheumatoid Arthritis ◽

Nitric Oxide ◽

Endothelial Dysfunction ◽

Disease Activity ◽

Proinflammatory Cytokines ◽

Inflammatory Disease ◽

No Production ◽

Tnf Α ◽

Relationship Of ◽

The Relationship

AbstractNitric oxide (NO) plays an important role in inflammatory joint disease and endothelial function. Endothelial dysfunction has been attributed to a reduction in NO bioactivity in rheumatoid arthritis (RA). However, the relationship of NO with inflammation and endothelial dysfunction in RA has not yet been investigated.To investigate the relationship of nitrite with inflammation and endothelial dysfunction in RA.Total 28 patients satisfying 2010 Rheumatoid Arthritis Classification Criteria were recruited for the study. Serum nitrite estimation was performed by Griess reaction. Flow-mediated dilation (FMD) assessed using AngioDefender. Inflammatory disease activity measures included disease activity score of 28 joints (DAS28), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Proinflammatory cytokines (TNF-α, IL-6, and IL-1) measured using standard ELISA kits. Twenty-five healthy controls matched for age and sex were included for comparison.The serum nitrite level in patients with RA was markedly elevated as compared with controls (p < 0.05). FMD was significantly impaired in RA patients than controls (p < 0.05). DAS28 was significantly higher in RA patients (p < 0.05). Levels of ESR, CRP, TNF-α, IL-1, and IL-6 were significantly higher in RA patients than controls (p < 0.05). Significant positive correlation was observed between nitrite and CRP (r = 0.46, p < 0.05), TNF-α (r = 0.53, p < 0.05), and inverse correlation with FMD (r =0.62, p < 0.05).Inflammatory disease activity and endothelial dysfunction in RA are associated with increased concentration of proinflammatory cytokines and NO. Inflammatory triggered release of cytokines induced NO production that mediates endothelial dysfunction. These findings suggest a role for NO in inflammation-induced endothelial dysfunction in RA.

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A mechanistic approach to understanding conjugated linoleic acid's role in inflammation using murine models of rheumatoid arthritis

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00005.2007 ◽

2007 ◽

Vol 293 (2) ◽

pp. R669-R676 ◽

Cited By ~ 22

Author(s):

Daniel E. Butz ◽

Guangming Li ◽

Shane M. Huebner ◽

Mark E. Cook

Keyword(s):

Rheumatoid Arthritis ◽

Corn Oil ◽

Joint Inflammation ◽

Arthritis Score ◽

Murine Models ◽

Collagen Induced Arthritis ◽

Naturally Occurring ◽

Mechanistic Approach ◽

Mediators Of Inflammation ◽

Anti Inflammatory

A naturally occurring fatty acid, conjugated linoleic acid (CLA), reduces immune-induced TNF and inducible cyclooxygenase (COX-2) expression; key mediators of inflammation in rheumatoid arthritis (RA). On the basis of previous work, it was hypothesized that dietary CLA would act as an anti-inflammatory agent in select animal models of RA. In the collagen antibody-induced arthritis (CAIA) model, mice fed CLA (mixed isomers of c9, t11, and t10, c12-CLA) for 3 wk before anticollagen antibody injection had reduced lipopolysaccharide-induced plasma TNF levels and had arthritic scores that were 60% of mice fed corn oil (CO). In the collagen-induced arthritis (CIA) model, mice fed mixed isomers of CLA for 21 days before immunization had lower IgG1 titers, earlier signs of joint inflammation, but similar arthritis scores compared with CO fed mice during the remaining 70-day post-injection period. Beginning on day 80 to 133, CLA-fed mice had arthritic scores 70% that of the CO-fed mice. In a second CIA experiment, CLA was fed only after the booster injection. Plasma IgG1 levels were not reduced and arthritis onset was delayed 4 days in CLA-fed mice compared with the CO-fed mice. Peak arthritis score was similar between CLA and CO-fed mice from day 35 to 56. Because CLA reduced inflammation in the CAIA model, delayed onset of arthritis in the CIA model (CIA experiment 2) and reduced arthritis score after day 80 in the CIA model (CIA experiment 1), we concluded that dietary CLA exhibited anti-inflammatory activity that was dependent on antibody.

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