Association of level of IL-6, IL-10, IL-18, tumour necrosis factor-α with rheumatic mitral stenosis and subsequent pulmonary hypertension

Background: Objective of the study was to provide insight on the immune response in patients of rheumatic heart disease, mitral stenosis and evaluation of various cytokines in pulmonary hypertension secondary to rheumatic heart disease.Methods: Total 163 subjects, more than 18 year of age, were enrolled in this study. 84 subjects with rheumatic mitral stenosis (group A) diagnosed on two-dimensional echocardiography (2D echo) and 79 normal healthy volunteers (group B). Patients with mitral stenosis were further divided into subgroups based on severity of mitral stenosis [mitral valve area (MVA >1 cm2 and MVA <1 cm2) (subgroup Aa and Ab)] and presence or absence of pulmonary hypertension [pulmonary arterial systolic pressure (PASP >36 mm Hg) (subgroup Ac and Ad)]. Interleukins IL-6, IL-10, IL-18, tumour necrosis factor alpha (TNF-α) and high-sensitivity C-reactive protein (hs-CRP) levels were assessed in both groups.Results: Mean IL-6, IL-10, IL-18, TNF-α and hs-CRP in group A and group B was 6.57±3.53 and 2.73±1 (p≤0.001), 8.185±2.8 and 3.51±0.86 (p≤0.001), 136.31±89.0 and 47.96±9.76 (p≤0.001), 21.26±18.59 and 5.36±3.57 (p≤0.001), 4.69±6.3 and 2.63±2.22 (p≤0.008) respectively. On subgroup analysis mean TNF-α in subgroup Aa was 20.71±16.84, while in subgroup Ab was 7.56±1.93 (p≤0.001). Mean IL-10 in subgroup Ac and Ad was 8.74±3.29 and 7.47±1.82, respectively. Differences in levels of other cytokines in these subgroups were not found statistically significant.Conclusions: This study finds increased IL-6, IL-10, IL-18, TNF-α and hs-CRP levels in subjects with rheumatic mitral stenosis. Subjects with severe mitral stenosis had increased TNF-α levels. Subjects of mitral stenosis having pulmonary hypertension had increased IL-10 levels.

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223 Association of levels of IL-6, IL-10, IL-18 and TNF-alpha with rheumatic mitral stenosis and subsequent pulmonary hypertension

European Heart Journal ◽

10.1093/ehjci/ehz872.008 ◽

2020 ◽

Vol 41 (Supplement_1) ◽

Author(s):

GAURAV Tripathi ◽

SANJAY Tyagi ◽

BHAWNA Mahajan ◽

VIMAL Mehta

Keyword(s):

Pulmonary Hypertension ◽

Mitral Stenosis ◽

Chronic Phase ◽

Public Health Problem ◽

Serum Levels ◽

Rheumatic Mitral Stenosis ◽

Tnf Α ◽

Group A ◽

Hs Crp ◽

Group B

Abstract Background Rheumatic heart disease (RHD) remains a serious public health problem in developing countries. The pattern of immune response after exposure to streptococcal infection is one of the main determinants of the rheumatic inflammatory process, making it essential to identify the patients who have a higher risk of disease progression. Objective To give an insight into the pathophysiology of the rheumatic afflicted valves and the role of IL-6, IL-10, IL-18 and TNF-α in the different stages of RHD. Methods The study included 84 consecutive patients (62 females, mean age 34.6 ± 10.6 years) with symptomatic, severe chronic rheumatic mitral stenosis (Group-A). 79 age and gender matched normal healthy volunteers were enrolled as controls (Group-B). Patients with chronic rheumatic mitral stenosis were further divided into subgroups based on severity of mitral stenosis [MVA ≤ 1 cm2 (Subgroup Aa) and MVA > 1 cm2 (Subgroups Ab)] and presence or absence of pulmonary hypertension [RVSP ≥ 36 mm Hg (Subgroup Ac) and RVSP < 36 mm Hg (Subgroup Ad)]. IL-6, IL-10, IL-18, TNF-α and hs-CRP levels were assessed in both groups. Results The mean serum levels of IL-6, IL-10, IL-18, TNF-α and hs-CRP in Group-A and Group-B were 6.57 ± 3.53 pg/mL and 2.73 ± 1.01 pg/mL (p <0.001), 8.19 ± 2.80 pg/mL and 3.51 ± 0.86 pg/mL (p <0.001), 136.31 ± 89.02 pg/mL and 47.96 ± 9.76 pg/mL (p <0.001), 21.26 ± 18.59 pg/mL and 5.36 ± 3.57 pg/mL (p <0.001), 4.69 ± 6.31 pg/mL and 2.63 ± 2.22 pg/mL (p <0.008) respectively. On subgroup analysis mean TNF-α in subgroup Aa was 20.71 ± 16.84 pg/mL, while in subgroup Ab it was 7.56 ± 1.93 pg/mL (p <0.001). Mean IL-10 in subgroup Ac and Ad was 8.74 ± 3.29 pg/mL and 7.47 ± 1.82 pg/mL respectively (p <0.028). Conclusions Chronic rheumatic mitral stenosis patients have increased IL-6, IL-10, IL-18, TNF-α and hs-CRP levels suggesting a continuous ongoing inflammatory activity even in chronic phase. Further subjects having severe mitral stenosis had increased TNF-α levels in comparison to subjects with mild to moderate mitral stenosis suggesting its possible role in acceleration of rheumatic process. Cytokines in various subgroup Parameter IL-6 (pg/ml) p IL-10 (pg/ml) p IL-18 (pg/ml) p TNF-α (pg/ml) p hs-CRP (pg/ml) p Subgroup Aa 5.63 ± 3.25 0.13 8.38 ± 3.06 0.32 146.35 ± 103.84 0.20 20.71 ± 16.84 <0.001 3.72 ± 3.43 0.67 Subgroup Ab 6.90 ± 3.57 7.72 ± 2.04 112.28 ± 22.79 7.56 ± 1.93 4.27 ± 3.81 Subgroup Ac 6.86 ± 3.50 0.44 8.74 ± 3.29 0.02 145.29 ± 103.01 0.29 20.25 ± 17.02 0.53 4.77 ± 0.93 0.93 Subgroup Ad 6.21 ± 3.49 7.47 ± 1.82 124.67 ± 66.95 22.91 ± 20.68 4.66 ± 3.44 Abstract 223 Figure. Cytokines in case and control

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Hospitalizations of Patients Treated with Anti-Tumor Necrosis Factor-α Agents — A Retrospective Cohort Analysis

The Journal of Rheumatology ◽

10.3899/jrheum.111516 ◽

2012 ◽

Vol 40 (1) ◽

pp. 16-22 ◽

Cited By ~ 13

Author(s):

DEVY ZISMAN ◽

AMIR HADDAD ◽

SHARBEL HASHOUL ◽

ARIE LAOR ◽

HAIM BITTERMAN ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Retrospective Cohort ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Cohort Analysis ◽

Tnf Α ◽

Group A ◽

Group B ◽

Factor Α ◽

Necrosis Factor

Objective.To assess the association between treatment with anti-tumor necrosis factor-α (TNF-α) agents and the occurrence of hospitalizations, their causes and complications, compared to treatment with traditional disease-modifying antirheumatic drugs in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS).Methods.A retrospective cohort study was conducted of patients with RA, AS, and PsA treated with anti-TNF-α agents between April 2002 and December 2007. Patients were assessed during the period of anti-TNF-α treatment (Group B) and compared to an equivalent period before initiation of anti-TNF-α therapy (Group A). All hospitalization charts were reviewed and diagnoses, comorbidities, concomitant medications, and clinical course were analyzed. Statistical analysis was performed using multivariate mixed Poisson regression.Results.In the study period of 57 months, 735 hospitalization events of 327 patients were analyzed. Statistically significant decreases were seen in the total number of hospitalization events as well as hospitalizations due to exacerbation of rheumatic diseases in Group B compared to Group A (44.4 vs 74.2 and 21.9 vs 47.5 per 100 patient-years, respectively; p < 0.0001). More infectious events (7.4 in Group B compared to 4.6 per 100 patient-years in Group A; p = 0.043) were associated with anti-TNF-α treatment, older age, and underlying disease, because patients with RA had higher rates of infections compared to patients with PsA and patients with AS.Conclusion.The overall effect of anti-TNF-α therapy was a significant decline in total hospitalization events. The decrease was more prominent in patients with RA than in patients with AS and patients with PsA, and reflected the significant decrease in hospitalizations due to rheumatic disease exacerbation. The decrease was more pronounced than the observed increase in infectious events.

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The Importance of Fever as a Predictive Symptom for the Potency of Host's Monocytes to Release Pro- and Anti-Inflammatory Mediators

Mediators of Inflammation ◽

10.1155/2008/450196 ◽

2008 ◽

Vol 2008 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Magdalini Kyriakopoulou ◽

Anastasia Antonopoulou ◽

Maria Raftogiannis ◽

Fotini Baziaka ◽

Thomas Tsaganos ◽

...

Keyword(s):

Inflammatory Mediators ◽

Tumour Necrosis ◽

Tumour Necrosis Factor Alpha ◽

Necrosis Factor Alpha ◽

Healthy Donors ◽

Group A ◽

Factor Alpha ◽

Anti Inflammatory ◽

Group B ◽

Necrosis Factor

Objective. To clarify whether time lapsing from advent of fever as a first sign of sepsis may be indicative of the potency of monocytes for the release of pro- and anti-inflammatory mediators.Methods. Monocytes were isolated from blood of 51 septic patients and 9 healthy donors. Monocytes were incubated in the absence and presence of patients' serum and concentrations of tumour necrosis factor-alpha (TNF), interleukin (IL)-6, IL-10, and malondialdehyde (MDA) were estimated in supernatants. Patients were divided into three groups: group A: 12 hours; group B: 12–24 hours, and group C: 24 hours between initiation of fever and blood sampling.Results. TNF of supernatants of groups B and C was higher than controls, as also were IL-6 of A and C, IL-10 of A and B, and MDA of A. IL-6 of group A was increased after addition of patients serum. A negative correlation was found between time from initiation of symptoms and IL-6 of monocyte supernatants incubated in the presence of patients serum. Median IL-6 of survivors was higher than nonsurvivors.Conclusion. Monocytes are potent for the release of pro- and anti-inflammatory mediators within the first 24 hours upon advent of fever related to sepsis; serum stimulates further release of IL-6 within the first 12 hours.

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Mao-to Prolongs the Survival of and Reduces TNF-α Expression in Mice with Viral Myocarditis

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nen010 ◽

2010 ◽

Vol 7 (3) ◽

pp. 341-349 ◽

Cited By ~ 2

Author(s):

Zhu Shijie ◽

Junji Moriya ◽

Jun’ichi Yamakawa ◽

Rui Chen ◽

Takashi Takahashi ◽

...

Keyword(s):

Survival Rates ◽

Viral Myocarditis ◽

Cardiac Damage ◽

Emc Virus ◽

Tnf Α ◽

Group A ◽

Group B ◽

Factor Α ◽

Group D ◽

Necrosis Factor

Goal of this study was to evaluate effects of Mao-to on development of myocarditis induced by encephalomyocarditis (EMC) virus in mice. Mice were randomly divided into five groups. Group N included uninfected controls (n= 18), while group A, B and C underwent intraperitoneal injection of EMC virus. Group A was administered oral saline from day 0 to day 4. Group B was administered oral Mao-to (500 mg−1kg−1day−1) from day 0 to day 4. Group C was administered Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10. Treated mice were followed for survival rates during 2 weeks after infection. Body weight (BW) and organ weights including heart (HW), lungs, thymus and spleen were examined on days 4, 6 and 14. Survival rate of group C (36.4%) was significantly improved compared with group A, B or D (0% of each,P< 0.05). HW and HW/BW ratio in group C was significantly (P< 0.05) lower than those in group A, B or D. Viral titers of hearts were significantly different among groups A, B and C. Cardiac expression in tumor necrosis factor-α (TNF-α) was significantly reduced in group C in comparison with group A, B or D on day 6 by immunohistochemical study. Administration of Mao-to starting on day 2 improves mortality resulting from viral myocarditis in mice with reduced expression of cardiac TNF-α. These findings suggest that timing of Mao-to is crucial for preventing cardiac damage in mice with viral myocarditis.

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ASSOCIATION OF LEVEL OF IL-6, IL-10, IL-18, TNF-α WITH RHEUMATIC MITRAL STENOSIS AND SUBSEQUENT PULMONARY HYPERTENSION

Indian Heart Journal ◽

10.1016/j.ihj.2018.10.079 ◽

2018 ◽

Vol 70 ◽

pp. S26

Author(s):

Gaurav Tripathi ◽

Vimal Mehta ◽

Vijay Trehan ◽

Puja Sakhuja ◽

Bhawna Mahajan ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Mitral Stenosis ◽

Rheumatic Mitral Stenosis ◽

Tnf Α

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Tumour Necrosis Factor-α Levels in Non-Diabetic Offspring of Patients with Type 2 Diabetes Mellitus

Journal of International Medical Research ◽

10.1177/147323000203000605 ◽

2002 ◽

Vol 30 (6) ◽

pp. 576-583 ◽

Cited By ~ 9

Author(s):

E Maltezos ◽

D Papazoglou ◽

T Exiara ◽

L Papazoglou ◽

E Karathanasis ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Tumour Necrosis Factor Α ◽

Tnf Α ◽

Group A ◽

Group B ◽

Factor Α ◽

Necrosis Factor

Tumour necrosis factor-α (TNF-α) is considered to be involved in the insulin resistance of type 2 diabetes mellitus. The offspring of patients with type 2 diabetes mellitus are at increased risk of developing diabetes and several metabolic abnormalities, but the underlying defects responsible are not known. We studied serum TNF-α levels in 30 healthy non-diabetic offspring of type 2 diabetic parents (group A), and the relationship between TNF-α levels and variables associated with insulin resistance and diabetes. For comparison, 30 healthy offspring of non-diabetic parents (group B) were also studied. The median serum concentration of TNF-α was significantly higher in group A than in group B, 3.5 pg/ml compared with 2.0 pg/ml, respectively. The individuals of group A also had significantly elevated levels of glycosylated haemoglobin, fasting glucose, glucose 2 h after an oral glucose tolerance test and triglycerides. We conclude that serum TNF-α concentration is significantly elevated in non-diabetic offspring of type 2 diabetics and this may predict later impairment of insulin action in these individuals.

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Correlation of Atrial Fibrillation with Left Atrial Volume in Patients with Mitral Stenosis. A single centre study from Pakistan

Pakistan Journal of Surgery and Medicine ◽

10.37978/pjsm.v1i1.105 ◽

2020 ◽

Vol 1 (1) ◽

pp. 23-28

Author(s):

Muhammad Arshad ◽

Furqan Yaqub Pannu ◽

Bilal Ahmad ◽

Salman Khalid ◽

Ahmad Kamran ◽

...

Keyword(s):

Atrial Fibrillation ◽

Mitral Valve ◽

Mitral Stenosis ◽

Left Atrial ◽

Left Atrial Volume ◽

Mitral Valve Stenosis ◽

Atrial Volume ◽

Group A ◽

Group B ◽

Rheumatic Heart

Background: Rheumatic heart disease has a strong association with mitral valve stenosis. Atrial fibrillation is one of the most common complications of this condition and is a poor prognostic factor. Early detection and prompt management of atrial fibrillation can help to improve the quality of life and increase the life expectancy of the patients. We carried out this study to investigate the significance of left atrial volumetric changes in mitral stenosis and its correlation with atrial fibrillation. Methodology: We audited the data of 60 patients of rheumatic heart disease who had mitral valve stenosis. The patients were randomized into atrial fibrillation (Group A) and normal sinus rhythm (Group B). We conducted this cross-sectional analytical study at Cardiology Department, Mayo Hospital, Lahore, from 1st February 2017 to 31st January 2018. We only included those patients who consented to be a part of this study and fulfilled our predefined inclusion criteria. Left atrial volume was measured by prolate ellipse method and biplane methods on echocardiography. The Data was analyzed on SPSS v20. Results: Sixty patients were included in the study. Among the subjects, thirty-six (60%) were males, and twenty-four (40%) were females. Atrial fibrillation was noted in 43.33% of the patients of mitral valve stenosis. There was a marked difference in the mean volume of the left atrium among the two groups. We observed that the mean area of the mitral valve for Group A patients was larger than that of patients in Group B. Our study showed an inverse correlation between left atrial volume and mitral valve area among Group A patients. Conclusion: Patients of mitral stenosis are at an increased risk of developing atrial fibrillation if the left atrial volume is increasing. All patients with mitral stenosis should have routine echocardiography & measurement of left atrial volumes, so that proper treatment can be started if the left atrial volume is increasing, to prevent atrial fibrillation.

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Posterior leaflet preservation during mitral valve replacement for rheumatic mitral stenosis

Acta chirurgica iugoslavica ◽

10.2298/aci0601013d ◽

2006 ◽

Vol 53 (1) ◽

pp. 13-17 ◽

Cited By ~ 1

Author(s):

P.L. Djukic ◽

B.B. Obrenovic-Kircanski ◽

M.R. Vranes ◽

M.J. Kocica ◽

A.Dj. Mikic ◽

...

Keyword(s):

Mitral Valve ◽

Valve Replacement ◽

Mitral Valve Replacement ◽

Mitral Stenosis ◽

Posterior Leaflet ◽

Rheumatic Mitral Stenosis ◽

Long Term Follow Up ◽

Group A ◽

Group B

Mitral valve replacement with posterior leaflet preservation was shown beneficial for postoperative left vetricular (LV) performance in patients with mitral regurgitation. Some authors find it beneficial even for the long term LV function. We investigated a long term effect of this technique in patients with rheumatic mitral stenosis. We studied 20 patents with mitral valve replacement due to rheumatic mitral stenosis, in the period from January 1988. to December 1989. In group A (10 patients) both leaflets and coresponding chordal excision was performed, while in group B (10 patients) the posterior leaflet was preserved. In all patients a Carbomedics valve was inserted. We compared clinical pre and postoperative status, as well as hemodynamic characteristics of the valve and left ventricle in both groups. Control echocardiographyc analysis included: maximal (PG) and mean (MG) gradients; effective valve area (AREA); telediastolic (TDV) and telesystolic (TSV) LV volume; stroke volume (SV); ejection fraction (EF); fractional shortening (FS) and segmental LV motion. The mean size of inserted valve was 26.6 in group A and 27.2 in group B. Hemodynamic data: PG (10.12 vs 11.1); MG (3.57 vs 3.87); AREA (2.35 vs 2.30); TDV 126.0 vs 114.5); TSV (42.2 vs 36.62); SV (83.7 vs 77.75); EF (63.66 vs 67.12); FS (32.66 vs 38.25) Diaphragmal segmental hypokinesis was evident in one patient from group A and in two patients from group B. In patients with rheumatic stenosis, posterior leaflet preservation did not have increased beneficial effect on left ventricular performance during long-term follow-up. An adequate posterior leaflet preservation does not change hemodynamic valvular characteristics even after long-term follow-up.

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Effects of Edaravone on Neurological Function and Tumor Necrosis Factor Alpha and Interleukin 8 Levels in Patients with Cerebral Infarction

European Neurology ◽

10.1159/000505776 ◽

2020 ◽

Vol 83 (1) ◽

pp. 73-79

Author(s):

Xiushan Li ◽

Dongzhou Ma ◽

Guozhu Sun

Keyword(s):

Cerebral Infarction ◽

Adverse Reactions ◽

Pearson Correlation ◽

Neurological Function ◽

Nihss Score ◽

Tnf Α ◽

Group A ◽

Pearson Correlation Analysis ◽

Group B ◽

Necrosis Factor

Objective: The present study aimed to explore the effects of edaravone on neurological function, tumor necrosis factor α (TNF-α), and interleukin (IL)-8 levels in patients with cerebral infarction. Methods: A total of 96 patients with cerebral infarction who were admitted to the department of neurology in our hospital were enrolled in the present study, and they were randomly assigned to Group A (n = 48) and Group B (n = 48). Group A was treated with conventional therapy plus edaravone for 2 weeks and Group B with conventional therapy alone for 2 weeks. Enzyme-linked immunosorbent assay was used to determine serum TNF-α and IL-8 levels before and after treatment, and Pearson correlation analysis was conducted to analyze the correlation between serum TNF-α and IL-8 levels as well as National Institutes of Health Stroke Scale (NIHSS) score. Results: After treatment, Group A had a lower NIHSS score and serum TNF-α and IL-8 levels as well as higher activities of daily living score than Group B (all p < 0.05). In addition, after treatment, no significant differences were observed between the 2 groups in terms of the presence of adverse reactions (p > 0.05). Pearson correlation analysis revealed a significant positive correlation between serum TNF-α and IL-8 levels as well as NIHSS score (r = –0.567 and r = –0.556, both p < 0.05). Conclusion: Edaravone can improve the neurological function of patients without causing evident adverse reactions, thereby improving quality of life, which may be correlated to decreased serum TNF-α and IL-8 levels.

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Prevalence and Predictors of Left Atrial Appendage Inactivity in patients of Rheumatic Mitral Stenosis in Sinus Rhythm- An observational study.

10.22541/au.162317425.57883810/v1 ◽

2021 ◽

Author(s):

Saibal Mukhopadhyay ◽

yogesh dwivedi ◽

Jamal Yusuf ◽

abhimanyu uppal ◽

VIMAL MEHTA

Keyword(s):

Mitral Valve ◽

Sinus Rhythm ◽

Mitral Stenosis ◽

Left Atrial ◽

Left Atrial Appendage ◽

Independent Predictor ◽

Atrial Appendage ◽

Rheumatic Mitral Stenosis ◽

Group A ◽

Group B

BACKGROUND: Systemic thromboembolism is a known complication of rheumatic mitral stenosis (RMS) in sinus rhythm (SR). Left atrial appendage (LAA), the commonest site of thrombus formation is usually hypocontractile (inactive) in such patients. We aimed to study the prevalence of LAA inactivity (LAAI) in severe RMS and assess its independent predictors. METHODS: The study population consisted of 100 patients of severe RMS in sinus rhythm. Transthoracic and transesophageal echocardiography were done to assess LAA contractile function. Patients with LAA-peak emptying velocity <25 cm/sec were defined as having LAAI. RESULTS: The mean age of study subjects was 31.66±8.69 years and 56% were females. 73% patients had LAAI (Group A), while remaining 27% had normal LAA function (Group B). Mitral-valve area (MVA) and lateral annulus systolic velocity (Sa-wave) were significantly lower while mean pressure gradient across mitral valve (MGMV) and serum fibrinogen were significantly higher (all p-values <0.001) in group A patients. On multivariate regression analysis, MGMV (p<0.001), Sa-wave (p=0.02) and serum fibrinogen (p=0.005) were independent predictors of LAAI. Optimal cut-off values of MGMV, Sa-wave and serum fibrinogen for predicting LAAI were 11.5mmHg, 6.8cm/sec and 300mg/dL respectively.67(90.55%) patients in group A compared to 13(48.1%) in group B had LA/LAA smoke. LAAI was the only independent predictor of left atrium (LA)/LAA smoke and associated thrombus. CONCLUSION: There is high prevalence of LAAI in patients of severe MS in SR. MGMV, Sa-wave and serum fibrinogen levels are independent predictors of LAAI. LAAI is an independent predictor of LA/LAA smoke and associated thrombus.

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