scholarly journals DYNAMICS OF CARDIOVASCULAR STATUS AND SERUM MARKERS OF ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH RHEUMATOID ARTHRITIS, TREATED WITH INFLIXIMAB

2013 ◽  
Vol 12 (2) ◽  
pp. 80-84
Author(s):  
S. P. Oranskyi ◽  
L. N. Eliseeva ◽  
N. A. Samorodskaya ◽  
I. G. Malkhasyan
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Dysfunction ◽  
Complex Dynamics ◽  
Interleukin 10 ◽  
Serum Markers ◽  
Left Ventricular ◽  
Infliximab Therapy ◽  
Lv Function ◽  
Doppler Flowmetry ◽  
Tnf Α

Aim. To assess the complex dynamics of the main parameters of cardiovascular status and serum markers of endothelial dysfunction (ED) in patients with rheumatoid arthritis (RA), who were treated with infliximab.Material and methods. The main group (MG) included 50 patients with seropositive RA, who received a combination of methotrexate and infliximab. The examination took place at baseline, as well as two, six, and 14 weeks after the treatment started. Comparison groups (CG) included healthy volunteers (n=25) and RA patients treated with methotrexate only (n=110). Serum levels of tumor necrosis factor-α (TNO-α), interleukin-10 (IL-10), tissue plasminogen activator (TPA), and von Willebrand factor (vWf) were measured, using ELISA. Left ventricular (LV) function and microvascular status were assessed with echocardiography and laser Doppler flowmetry (LDF), respectively.Results. The E/A ratio was reduced in all subgroups, and at Week 14 of infliximab therapy, it slightly increased. At baseline, LDF parameters, such as neurogenic arteriole tone and intravascular resistance, were increased. Infliximab therapy was associated with a moderate decline of these parameters. Throughout the study, serum vWf concentration was higher in MG patients than in healthy controls. TPA activity was reduced at baseline (496±173 pg/ml), increasing at Week 14 up to 705±157 pg/ml. Baseline concentrations of TNF-α and UL-10 were substantially elevated (357,1±34 and 453±42 pg/ml, respectively). At Week 6, TNF-α concentration decreased significantly. At Week 14, not only TNF-α level decreased, reaching 94±28 pg/ml, but also the ratio TNF-α/IL-10 decreased (from 0,78±0,5 to 0,4±0,2).Conclusion. In RA patients, infliximab was highly effective for the functional cytokine dysbalance correction, also demonstrating pleiotropic effects, such as correction of microvascular and endothelial dysfunction. 

scholarly journals Anti–TNF-α therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-β

2007 ◽  
Vol 204 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Suchita Nadkarni ◽  
Claudia Mauri ◽  
Michael R. Ehrenstein
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cell Population ◽  
Transforming Growth Factor ◽  
Cell Subset ◽  
Interleukin 10 ◽  
Infliximab Therapy ◽  
Tnf Α ◽  
Necrosis Factor

The induction of regulatory T (T reg) cells holds considerable potential as a treatment for autoimmune diseases. We have previously shown that CD4+CD25hi T reg cells isolated from patients with active rheumatoid arthritis (RA) have a defect in their ability to suppress proinflammatory cytokine production by CD4+CD25− T cells. This defect, however, was overcome after anti–tumor necrosis factor (TNF)-α antibody (infliximab) therapy. Here, we demonstrate that infliximab therapy gives rise to a CD4+CD25hiFoxP3+ T reg cell population, which mediates suppression via transforming growth factor (TGF)-β and interleukin 10, and lacks CD62L expression, thereby distinguishing this T reg cell subset from natural T reg cells present in healthy individuals and patients with active RA. In vitro, infliximab induced the differentiation of CD62L− T reg cells from CD4+CD25− T cells isolated from active RA patients, a process dependent on TGF-β. In spite of the potent suppressor capacity displayed by this CD62L− T reg cell population, the natural CD62L+ T reg cells remained defective in infliximab-treated patients. These results suggest that anti–TNF-α therapy in RA patients generates a newly differentiated population of T reg cells, which compensates for the defective natural T reg cells. Therefore, manipulation of a proinflammatory environment could represent a therapeutic strategy for the induction of T reg cells and the restoration of tolerance.

Astragaloside attenuates cardiotoxicity effects of Doxorubicin by inhibiting TLR4/NF-кB signaling pathway

2017 ◽  
Vol 5 (1) ◽  
pp. 93-108
Author(s):  
Russell Nahorski ◽  
Arnim Ploeger
Keyword(s):  
Protein Expression ◽  
Treated Group ◽  
Left Ventricular ◽  
Lv Function ◽  
Total Protein Content ◽  
Limiting Factor ◽  
Transverse Diameter ◽  
Protective Effects ◽  
Tlr4 Mrna ◽  
Tnf Α

Doxorubicin (DOX) is one of the most widely used and successful antitumor drugs, but its cumulative and dose-dependent cardiac toxicity has been the major concern of oncologists in cancer therapeutic practice for decades. Cardiotoxicity is a major limiting factor in anticancer therapy. Astragaloside (Ast) is one of the main effective components isolated from the traditional Chinese medical herb Astragalus membranaceus. The possible protective effects Ast against cardiotoxicity were investigated in wild type C57BL/6 mice treated with saline, saline+doxorubicin (DOX; 20 mg/kg) or Ast (20 mg/kg)+DOX continued for a period of 5 weeks. The cardiomyopathy was assessed using transthoracic echocardiography before the start of treatment and after 14 days and plasma lactate dehydrogenase (LDH) activity was measured after 14 days. Cardiac catheterizations for assessments LV function before the mice were decapitated. To measure the transverse diameter of left ventricular myocardial cells (TDM), the hematoxylin-eosin (HE) staining method was applied. In addition, the volume and the total protein content of cardiomyocytes were measured, the mRNA expression of ANP and TLR4 were quantified by RT-PCR, the protein expression of TLR4, IκBα and p65 were quantified by Western blot, and the level of TNF-α and IL-6 were measured by ELISA. Ast treatment demonstrated improved LV function, TDM were significantly decreased; the protein expression of TLR4 and p65 were reduced, while the IκBα were increased; the expression of ANP, TLR4 mRNA, and TNF-α, IL-6 in serum were significantly reduced compared with the doxorubicin-treated group. The study suggests that Ast may have a potential protective role against doxorubicin-induced cardiotoxicity in mice.

scholarly journals Interleukin-10 inhibits the in vivo and in vitro adverse effects of TNF-α on the endothelium of murine aorta

2010 ◽  
Vol 299 (4) ◽  
pp. H1160-H1167 ◽  
Author(s):  
Saiprasad M. Zemse ◽  
Chin Wei Chiao ◽  
Rob H. P. Hilgers ◽  
R. Clinton Webb
Keyword(s):  
Endothelial Dysfunction ◽  
Interleukin 10 ◽  
Enos Expression ◽  
Response Curves ◽  
Female Mice ◽  
In Vivo Experiments ◽  
Tnf Α ◽  
Significant Impairment

TNF-α is a proinflammatory cytokine and is an important mediator of maternal endothelial dysfunction leading to preeclampsia. In this study, we tested whether IL-10 protects against TNF-α-induced endothelial dysfunction in murine aorta. In in vitro experiments, aortic rings of C57BL/6 female mice were incubated in Dulbecco's modified Eagle's medium in the presence of either vehicle (distilled H2O), TNF-α (4 nmol/l), or recombinant mouse IL-10 (300 ng/ml) or in the presence of both TNF-α and IL-10 for 22 h at 37°C. In in vivo experiments C57BL6/IL-10 knockout female mice were treated with saline or TNF-α (220 ng·kg−1·day−1) for 14 days. Aortic rings were isolated from in vitro and in vivo experiments and mounted in a wire myograph (Danish Myotech) and stretched to a tension of 5 mN. Endothelium-dependent relaxation was assessed by constructing cumulative concentration-response curves to acetylcholine (ACh, 0.001–10 μmol/l) during phenylephrine (10 μmol/l)-induced contraction. As a result, overnight exposure of aortic rings to TNF-α resulted in significant blunted maximal relaxing responses ( Emax) to ACh compared with untreated rings (22 ± 4 vs. 82 ± 3%, respectively). IL-10 knockout mice treated with TNF-α showed significant impairment in ACh responses ( Emax) compared with C57BL/6 mice treated with TNF-α (51 ± 3 vs. 72 ± 3%, respectively). Western blot analysis showed that endothelial nitric oxide synthase (eNOS) expression was reduced by TNF-α in in vitro and in vivo experiments, whereas IL-10 restored the eNOS expression. In conclusion, the anti-inflammatory cytokine IL-10 prevents impairment in endothelium-dependent vasorelaxation caused by TNF-α by protecting eNOS expression.

scholarly journals Left ventricular function in rheumatoid arthritis during anti-TNF-α treatment: a speckle tracking prospective echocardiographic study

2016 ◽  
Vol 84 (1-2) ◽  
Author(s):  
Enrico Vizzardi ◽  
Ilaria Cavazzana ◽  
Franco Franceschini ◽  
Ivano Bonadei ◽  
Edoardo Sciatti ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Heart Failure ◽  
Speckle Tracking ◽  
Longitudinal Strain ◽  
Systolic Function ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Cardiac Complications ◽  
Tnf Α ◽  
One Year

<p><strong>Aim</strong>. Rheumatoid arthritis (RA) shows a high risk for cardiovascular disease, including heart failure. Although TNF-α has been implicated in the pathogenesis of myocardial remodelling, TNF-α inhibition did not show any efficacy in patients with advanced heart failure and should be contraindicated in RA with cardiac complications. We aimed to assess global left ventricular (LV) systolic function using global longitudinal strain (GLS) as a measure of myocardial deformation, in a group of RA patients before and during anti-TNF-α treatment. <strong>Methods</strong>. 13 patients (female:male 7:6) affected by RA were prospectively followed for one year during anti TNF-α treatment. Every subject underwent echocardiography before starting anti-TNF-α drugs and after one year of treatment, to evaluate LV ejection fraction (EF), telediastolic diameter, telediastolic volume and global longitudinal strain (GLS) that was calculated using 2D speckle tracking as the mean GLS from three standard apical views (2, 3 and 4 -chambers). The patients showed a mean age of 43 years at RA onset (SD: 13) and a mean follow-up of 7.3 years (SD: 4.8). Steroid and methotrexate were used in 84.6% and 100%, respectively, in association with etanercept (6 cases), adalimumab (4 cases) and infliximab (3 cases). <strong>Results</strong>. Patients globally showed a normal EF before and after one year of treatment (mean: 65% and 65.7%, respectively). GLS did not differ before or after anti-TNF-α treatment (mean: -15.8% and -16.7%, respectively). <strong>Conclusion</strong>. Anti-TNF-α treatment did not significantly modify myocardial contractility after 12 months.</p><p> </p><p> </p>

Infliximab Treatment Increases Left Ventricular Ejection Fraction in Patients with Rheumatoid Arthritis: Assessment of Heart Function by Echocardiography, Endothelin 1, Interleukin 6, and NT-pro Brain Natriuretic Peptide

2012 ◽  
Vol 39 (4) ◽  
pp. 701-706 ◽  
Author(s):  
PRZEMYSLAW J. KOTYLA ◽  
ALEKSANDER OWCZAREK ◽  
JAROSLAW RAKOCZY ◽  
MACIEJ LEWICKI ◽  
EUGENE J. KUCHARZ ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Brain Natriuretic Peptide ◽  
Disease Activity ◽  
Interleukin 6 ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Tnf Α

Objective.To study the influence of anti-tumor necrosis factor-α (TNF-α) treatment on echocardiographic measures and concentrations of endothelin 1 (ET-1), interleukin 6 (IL-6), and amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in a cohort of 23 female patients with rheumatoid arthritis (RA).Methods.We recruited 23 patients (mean age 51.3 ± 1.55 yrs) with RA resistant to treatment with disease-modifying antirheumatic drugs and average disease duration of 7.1 ± 1.0 years who had been selected to start treatment with the anti-TNF-α antagonist infliximab. Transthoracic echocardiographic examinations were performed before the first infusion and repeated after 1 year of treatment. Data for age, sex, RA disease activity by Disease Activity Score (DAS28) and echocardiographic data, NT-proBNP, IL-6, ET-1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and other routine laboratory data were collected before treatment and after 1 year.Results.Twelve months of treatment with infliximab resulted in reduction of RA activity (i.e., reduction of DAS and acute-phase reactants). There was increased left ventricle ejection fraction, from 58.5% before treatment to 63% after. Treatment with infliximab also resulted in significant reduction of ET-1 (1.26 fmol/ml before treatment vs 0.43 fmol/ml after), IL-6 (58.46 pg/ml vs 3.46 pg/ml), and NT-proBNP (43.06 fmol/ml vs 14.78 fmol/ml). These reductions were observed after just 4 months of treatment and remained significant until the termination of the study.Conclusion.In patients with RA, treatment with infliximab contributed significantly to increase in left ventricular ejection fraction. Improvement of cardiac function was shown by conventional echocardiography; there was reduction of biochemical markers of heart failure.

Vitamin C and quinapril abrogate LVH and endothelial dysfunction in aortic-banded guinea pigs

2001 ◽  
Vol 281 (4) ◽  
pp. H1704-H1710 ◽  
Author(s):  
John P. Bell ◽  
Salah I. Mosfer ◽  
Derek Lang ◽  
Francis Donaldson ◽  
Malcolm J. Lewis
Keyword(s):  
Body Weight ◽  
Endothelial Dysfunction ◽  
Vitamin C ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Antioxidant Vitamin ◽  
Ang Ii ◽  
Text Production ◽  
Tnf Α

Left ventricular hypertrophy (LVH) is a cardiovascular risk factor. A possible role for endothelial dysfunction in this condition was investigated in a Dunkin-Hartley guinea pig aortic-banded pressure overload-induced model of LVH. Aortic banding produced significant elevation of fore- and hindlimb blood pressure (BP), heart-to-body weight ratios, plasma angiotensin II (ANG II), endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α) levels, and coronary microvascular endothelial cell (CMEC) NAD(P)H-dependent superoxide (O[Formula: see text]) production, and a significant decrease in basal and stimulated CMEC cGMP levels. Treatment of aortic-banded animals with the angiotensin-converting enzyme inhibitor quinapril and the antioxidant vitamin C, either alone or in combination, did not affect BP but caused a significant inhibition of the increases in the heart-to-body weight ratio, ANG II, ET-1, and TNF-α levels, and O[Formula: see text] production and restored cGMP responses to levels comparable with sham-operated animals. These data suggest that quinapril and vitamin C are capable of inhibiting LVH development due to pressure overload via mechanisms that involve the inhibition of oxidative stress, an improvement in coronary endothelial function, and increased nitric oxide bioavailability.

Association of soluble apoptotic markers with impaired left ventricular deformation in patients with rheumatoid arthritis. Effects of inhibition of interleukin-1 activity by anakinra

2011 ◽  
Vol 106 (11) ◽  
pp. 959-967 ◽  
Author(s):  
Ignatios Ikonomidis ◽  
Stavros Tzortzis ◽  
John Lekakis ◽  
Ioannis Paraskevaidis ◽  
Pinelopi Dasou ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Fas Ligand ◽  
Interleukin 1 ◽  
Left Ventricular ◽  
Experimental Myocardial Infarction ◽  
Caspase 9 ◽  
Double Blind ◽  
Left Ventricular Deformation ◽  
Apoptotic Markers ◽  
Tnf Α

SummaryMyocardial function is impaired in rheumatoid arthritis (RA). Inhibition of interleukin (IL)-1 activity reduces experimental myocardial infarction by limiting apoptosis. We investigated whether a) soluble apoptotic markers are related with impaired left ventricular (LV) performance and b) treatment with anakinra, an IL-1 receptor antagonist, reduces apoptotic markers leading to improved LV performance in RA. We studied 46 RA patients. In an acute, double-blind cross-over trial, 23 patients were randomised to a single injection of anakinra or placebo and after 48 hours (h) to the alternative treatment. In a chronic trial, 23 patients who received anakinra for 30 days were compared with 23 patients who received prednisolone. At baseline, 3 h and 30 days after treatment, we measured circulating IL-1β, tumour necrosis factor (TNF)-α, Fas, Fas-ligand and caspase-9 to assess apoptosis. At baseline and 30 days after treatment, we assessed LV longitudinal strain, strain rate and E/Em ratio using 2D-speckle tracking and tissue Doppler echocardiography. At baseline, increased apoptotic markers were related with reduced LongSRS and increased E/Em (p<0.05). After 3 h and 30 days of anakinra, there was a reduction in Fas (median 481 vs. 364 vs. 301 pg/ml), Fasligand (median 289 vs. 221 vs. 190 pg/ml), caspase-9 (median 1.90 vs. 1.40 vs. 1.07 ng/ml), TNF-α and IL-1β (p<0.05 for all comparisons). E/Em, LongS and LongSRS were improved after anakinra (p<0.01) and their percent changes were related with the corresponding changes of Fas and caspase-9 (p<0.05). No changes of the examined parameters were observed after prednisolone. In conclusion, inhibition of IL-1 activity by anakinra reduces apoptotic markers leading to improved LV performance in RA.

Interleukin 10 and Tumor Necrosis Factor-α Genotypes in Rheumatoid Arthritis — Association with Clinical Response to Glucocorticoids

2010 ◽  
Vol 37 (3) ◽  
pp. 503-511 ◽  
Author(s):  
BANESA de PAZ ◽  
MERCEDES ALPERI-LÓPEZ ◽  
FRANCISCO J. BALLINA-GARCÍA ◽  
CATUXA PRADO ◽  
LOURDES MOZO ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Clinical Response ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 10 ◽  
Functional Polymorphisms ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective.There are dysregulated levels of interleukin 10 (IL-10) and tumor necrosis factor-α (TNF-α) in rheumatoid arthritis (RA), and their role in the disease is controversial. We analyzed the association of functional polymorphisms of IL-10 and TNF-α with susceptibility and disease characteristics at the time of diagnosis, and we also evaluated their possible use as predictors of clinical response to treatments.Methods.Patients with recent-onset RA (n = 162) and healthy controls (n = 373) were genotyped for −1082 IL-10 and −308 TNF-α polymorphisms and data were related to clinical and immunological measurements of patients at the time of diagnosis. Response to treatment after 6 months was determined in 125 patients by the absolute change in Disease Activity Score (DAS28) and the American College of Rheumatology criteria for improvement.Results.We found a reduced frequency of the low IL-10 producer genotype (−1082AA) in patients with RA compared to controls (26.5% vs 38.9%; p = 0.006), while it is a risk factor for anticyclic citrullinated peptide antibodies (anti-CCP) positivity (p = 0.028). Evaluation of clinical response to treatments indicated that carriage of the high IL-10 genotype was associated with a favorable outcome (p = 0.009), specifically to prednisone therapy (p = 0.0003). No significant effects were observed with TNF-α polymorphism alone; however, in combination with the IL-10 genotype, it increased the strength of these associations.Conclusion.Results show an association between the low IL-10 producer genotype and protection from RA; nevertheless, when other specific genetic and/or environmental factors trigger onset of RA, this genotype may predispose to development of anti-CCP+ RA disease with reduced response to prednisone treatment.

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