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

2016 ◽  
Vol 26 (03) ◽  
pp. 165-169 ◽  
Author(s):  
Nidhi Garg ◽  
Ashit Syngle ◽  
Pawan Krishan

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.

Rheumatology ◽  
1984 ◽  
Vol 23 (1) ◽  
pp. 15-19 ◽  
Author(s):  
J. G. LARKIN ◽  
G. D. O. LOWE ◽  
R. D. STURROCK ◽  
C. D. FORBES

1998 ◽  
Vol 66 (12) ◽  
pp. 5792-5798 ◽  
Author(s):  
Keiji Funatogawa ◽  
Motohiro Matsuura ◽  
Masayasu Nakano ◽  
Makoto Kiso ◽  
Akira Hasegawa

ABSTRACT Lipid A is the active center of bacterial lipopolysaccharide (LPS), which exhibits diverse biological activities via the production of various mediators. We investigated the production of nitric oxide (NO), one of the mediators, by a murine macrophage cell line, RAW264.7, upon stimulation with a series of monosaccharide lipid A analogues to elucidate the relationship of structure and activity in NO production. The production of other representative mediators, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), was also investigated to compare the structural requirements for the production of these cytokines with those for the production of NO. Structure-activity relationships in NO production correlated well with those in the production of TNF-α and IL-6. Among the lipid A analogues possessing different numbers of acyl groups on a 4-O-phosphono-d-glucosamine backbone, compounds like GLA-60 that possess three tetradecanoyl (C14) groups exhibited stronger activities in the production of the mediators than compounds possessing four or two C14 groups. Time course study of the production of these mediators showed that production of NO started and peaked later than those of TNF-α and IL-6. Neither neutralization of TNF-α activity by antibody nor suppression of TNF-α production by pentoxifylline showed a significant suppressive effect on production of NO and IL-6 upon stimulation with LPS or lipid A analogues. Neutralization of IL-6 activity by antibody showed no significant suppressive effect on production of NO and TNF-α. A monosaccharide lipid A analogue (GLA-58) which exhibited no detectable agonistic activity showed a suppressive effect on the production of all three mediators upon stimulation with LPS or lipid A analogues. These results indicate that signals for NO production by LPS agonists in murine macrophages are transduced in good correlation with those for production of TNF-α and IL-6, although they are not transduced via production of those cytokines.


Folia Medica ◽  
2017 ◽  
Vol 59 (1) ◽  
pp. 37-42 ◽  
Author(s):  
Maria H. Kazakova ◽  
Anastas Z. Batalov ◽  
Nonka G. Mateva ◽  
Zlatimir G. Kolarov ◽  
Victoria S. Sarafian

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.


Medicina ◽  
2020 ◽  
Vol 56 (10) ◽  
pp. 545
Author(s):  
Khai-Jing Ng ◽  
Hui-Chun Yu ◽  
Hsien-Yu Huang Tseng ◽  
Chia-Wen Hsu ◽  
Ming-Chi Lu

Background and objectives: To investigate the serum procalcitonin (PCT) levels among patients with rheumatoid arthritis (RA) without active infection compared with healthy controls and to understand the relationship of PCT with RA disease activity, and treatment received by patients. Materials and Methods: Patients aged 20 years and above with clinician-confirmed diagnosis of RA and healthy volunteers were included during regular outpatient visits, and those with active infection symptoms and signs were excluded. RA disease activity was measured using the Disease Activity Score-28 for Rheumatoid Arthritis with erythrocyte sedimentation rate (DAS28-ESR). Medications received by the patients were also recorded. Results: A total of 623 patients with RA and 87 healthy subjects were recruited in this study. The mean PCT were significantly higher in patients with RA (6.90 ± 11.81 × 10−3 ng/mL) compared with healthy controls (1.70 ± 6.12 × 10−3 ng/mL) (p < 0.001) and the difference remained statistically significant after adjusting for age and sex. In addition, multiple linear regression analysis showed that a lower rank-transformed PCT serum level was significantly correlated with the use of biologics (p = 0.017) and a high DAS28-ESR score (p = 0.028) in patients with RA. Conclusion: Patients with RA have a significantly higher serum PCT levels compared with healthy controls. The use of biologics and an active RA disease activity were associated with a lower level of PCT in patients with RA. Further investigation is required to determine the optimal cutoff value of PCT among patients with RA and its association with disease activity and biologic usage.


2020 ◽  
Vol 7 ◽  
Author(s):  
Irene Llorente ◽  
Noelia García-Castañeda ◽  
Cristina Valero ◽  
Isidoro González-Álvaro ◽  
Santos Castañeda

Osteoporosis has been classically considered a comorbidity of rheumatoid arthritis (RA). However, recent advances in the pathogenesis of osteoporosis in RA have shown a close interplay between cells of the immune system and those involved in bone remodeling, introducing new actors into the classic route in which osteoclast activation is related to the RANK/RANKL/OPG pathway. In fact, the inflammatory state in early stages of RA, mediated by interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-α has the ability to activate and differentiate osteoclasts not only through their relationship with RANKL, but also through the Wnt/DKK1/sclerostin pathway, leading to bone loss. The role of synovial fibroblasts and activated T lymphocytes in the expression of the RANKL system and its connection to bone destruction is also depicted. In addition, autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are other pathogenic mechanisms for the development of bone erosions and systemic osteoporosis in RA, even before the onset of arthritis. The aim of this review is to unravel the relationship between different factors involved in the development of osteoporosis in RA patients, both the classic factors and the most novel, based on the relationship of autoantibodies with bone remodeling. Furthermore, we propose that bone mineral density measured by different techniques may be helpful as a biomarker of severity in early arthritis patients.


2021 ◽  
Vol 93 (5) ◽  
pp. 581-586
Author(s):  
Olga V. Dobrovolskaya ◽  
Natalia V. Toroptsova ◽  
Oksana A. Nikitinskaya ◽  
Elena Y. Samarkina ◽  
Mariia V. Cherkasova ◽  
...  

Aim. To evaluate the status of vitamin D in women with rheumatoid arthritis (RA) and establish its associations with comorbidity, disease activity, and body composition components. Materials and methods. 86 women with RA (average age 58.18.5 years) were enrolled in the study. We analyzed the relationship of vitamin D levels with clinical and laboratory parameters and with the results of two-energy x-ray absorptiometry. MannWhitney or KruskalWallis, 2 and Spearman tests were performed using Statistica for Windows 10.0 (StatSoft Inc., USA). Results. Vitamin D level was 22.4 [17.8; 27.3] ng/ml: deficiency was detected in 33%, and insufficiency in 46% of women with RA. Only 41% of patients with low vitamin D levels received supplements of cholecalciferol, while only 9% in a sufficient dose. 25(OH)D level was significantly lower in RA patients with sarcopenia, obesity, high activity according to DAS28 and in those who did not receive vitamin D supplements. There werent differences in 25(OH)D levels among subgroups of patient according to age, fertility, BMD status, comorbidity index, RA duration, ESR and CRP levels, medical therapy performed. Conclusion. 79% of patients with RA had low levels of vitamin D, while less than half of them received additional cholecalciferol supplements. Low vitamin D levels in RA patients were associated with high disease activity, sarcopenia, and obesity.


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