The impact of anti-inflammatory cytokines provoked by CD163 positive macrophages on ventricular functional recovery after myocardial infarction

Stem cells transplantation is being explored as an effective therapy for heart diseases. However, majority of stem cell therapies for adult patients with myocardial infarction (MI) had mixed and inconsistent results implying chronological age may influence the effectiveness of regenerative therapies. Therefore, herein, we performed a head-to-head comparison between different, well-studied stem cell types to identify the superior regenerative cell type using rodent MI model.After our standard characterization for each stem cell type (FACS for cell surface markers), 1 million neonatal Cardiac Mesenchymal Stem cells (nMSCs), adult MSCs (aMSCs), adult derived cardiosphere derived cells (aCDCs), umbilical cord derived cells (UCBCs), Bone Marrow derived Mesenchymal Stem cells (BM-MSCs), or cell-free Iscove Modified Dulbecco Medium (IMDM as placebo control) were injected into athymic rat myocardial infarct model. Although all the tested groups significantly improved ejection fraction, nMSCs outperformed other stem cells in cardiac functional recovery. Additionally, nMSCs also showed significant increased cardiac functional recovery compared to aMSCs in wild type rat MI model. Mason trichrome staining with heart sections revealed that decreased fibrosis was evident on nMSCs injection compared to aMSCs in both athymic and wild type rat MI model. Myocardial sections from rats received nMSCs showed significantly reduced M1 macrophages (inflammatory) and increased M2 macrophages (anti-inflammatory) compared with sections from rats having received aMSCs and IMDM control. Pro and anti-inflammatory cytokines analyzed on sera collected on day 2 and 7 revealed that anti-inflammatory cytokine (IL10) was significantly increased and inflammatory cytokines (IL4 and IL12) reduced in nMSCs compared to aMSCs transplanted MI rat model.In conclusion, nMSCs demonstrated superior functional abilities, reduced fibrosis, inflammatory cells and cytokines compared to all the other cell types and with aMSCs demonstrating that nMSCs is an ideal stem cell type for therapeutic application in myocardial infarction.

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Differential Effector Response of Amnion- and Adipose-Derived Mesenchymal Stem Cells to Inflammation; Implications for Intradiscal Therapy

10.1101/523001 ◽

2019 ◽

Author(s):

Ryan Borem ◽

Allison Madeline ◽

Mackenzie Bowman ◽

Sanjitpal Gill ◽

John Tokish ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Inflammatory Cytokines ◽

Optimal Choice ◽

Human Mscs ◽

Tissue Destruction ◽

Effector Functions ◽

Anti Inflammatory ◽

Factor Α ◽

The Impact

ABSTRACTIntervertebral disc degeneration (IVDD) is a progressive condition marked by inflammation and tissue destruction. The effector functions of mesenchymal stem cells (MSCs) make them an attractive therapy for patients with IVDD. While several sources of MSCs exist, the optimal choice for use in the inflamed IVD remains a significant question. Adipose (AD)- and amnion (AM)-derived MSCs have several advantages compared to other sources, however, no study has directly compared the impact of IVDD inflammation on their effector functions. Human MSCs were cultured in media with or without supplementation of interleukin-1β and tumor necrosis factor-α at concentrations produced by IVDD cells. MSC proliferation and production of pro- and anti-inflammatory cytokines were quantified following 24- and 48-hours of culture. Additionally, the osteogenic and chondrogenic potential of AD- and AM-MSCs was characterized via histology and biochemical analysis following 28 days of culture. In inflammatory culture, AM-MSCs produced significantly more anti-inflammatory IL-10 (p=0.004) and larger chondrogenic pellets (p=0.04) with greater percent area staining positively for glycosaminoglycan (p<0.001) compared to AD-MSCs. Conversely, AD-MSCs proliferated more resulting in higher cell numbers (p=0.048) and produced higher concentrations of pro-inflammatory cytokines PGE2 (p=0.030) and IL-1β (p=0.010) compared to AM-MSCs. Additionally, AD-MSCs produced more mineralized matrix (p<0.001) compared to AM-MSCs. These findings begin to inform researchers and clinicians as to which MSC source may be optimal for different IVD therapies including those that may promote regeneration or fusion. Further study is warranted evaluating these cells in systems which recapitulate the nutrient- and oxygen-deprived environment of the degenerate IVD.

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Role of Pro-/Anti-Inflammatory Cytokines and their Correlation with Established Risk Factors in South Indians with Coronary Artery Disease

Angiology ◽

10.1177/0003319708321101 ◽

2008 ◽

Vol 60 (4) ◽

pp. 419-426 ◽

Cited By ~ 13

Author(s):

Medha Rajappa ◽

S. K. Sen ◽

Alpana Sharma

Keyword(s):

Myocardial Infarction ◽

Coronary Artery Disease ◽

Acute Myocardial Infarction ◽

Coronary Artery ◽

Unstable Angina ◽

Inflammatory Cytokines ◽

Tumor Necrosis ◽

Interleukin 10 ◽

Anti Inflammatory ◽

Artery Disease

Cytokines are responsible for the modulation of immunological and inflammatory processes and play a significant role in the pathogenesis of coronary artery disease. We estimated the levels of pro-/anti-inflammatory cytokines in South Indian patients with coronary artery disease. The study population comprised of groups 1–3: 100 patients each with acute myocardial infarction, unstable angina, and stable angina, respectively, and group 4 (100 healthy controls). Cytokine levels (interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α) were estimated by enzyme-linked immunosorbent assay (ELISA). Interleukin-6, interleukin-8, and tumor necrosis factor-α levels were significantly higher in patients from groups 1 and 2, than in group 3 and controls. Acute myocardial infarction patients exhibited higher serum levels of interleukin-10 compared with other groups and control subjects. Patients with unstable angina had significantly lower interleukin-10 concentrations than those with stable angina. The ratios of pro-/anti-inflammatory cytokines in all the study groups increased significantly when patients with unstable angina were compared to other groups. In patients with acute myocardial infarction, interleukin-10 and tumor necrosis factor-α levels showed significant correlation with established risk factors such as body mass index, blood pressure, and lipid levels. Acute myocardial infarction patients show elevation in proinflammatory and anti-inflammatory cytokines, while unstable angina is associated with low levels of serum interleukin-10. Higher levels of antiinflammatory cytokine interleukin-10 may be needed to provide protection in unstable angina. These cytokines are markers of coronary artery disease and may be used for the identification of high-risk patients with unstable angina/acute myocardial infarction.

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Prognostic impact of elevated baseline CRP levels in primary PCI-treated patients with residual cholesterol risk

European Heart Journal ◽

10.1093/ehjci/ehaa946.1563 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

V Zobenica ◽

D Milasinovic ◽

D Jelic ◽

Z Mehmedbegovic ◽

S Zaharijev ◽

...

Keyword(s):

Myocardial Infarction ◽

Cox Regression ◽

Density Lipoprotein ◽

Prognostic Impact ◽

Primary Pci ◽

Killip Class ◽

Reference Limit ◽

Tertiary Center ◽

Anti Inflammatory ◽

The Impact

Abstract Background Recent large randomized studies have indicated the potential of anti-inflammatory therapies to reduce adverse cardiovascular events in patients with myocardial infarction, with the most pronounced benefit in patients with baseline elevated C-reactive protein (CRP). Purpose Our aim was to assess the association of CRP levels with 30-day and 1-year mortality in patients with acute myocardial infarction treated with primary PCI and with residual cholesterol risk. Methods The study included 1531 patients admitted for primary PCI, with the residual cholesterol risk, i.e. low-density lipoprotein cholesterol (LDL-C) levels of >1.80 mmol/l (70 mg/dl), from a prospectively kept electronic registry of a high-volume tertiary center, for whom in-hospital CRP measurements were available. Elevated CRP was defined as ≥5 mg/l (local laboratory cut off value), measured during index hospitalization. Cox regression models were constructed to assess the impact of elevated CRP on 30-day and 1-year mortality. Results 72% of the included patients with LDL-C >1.80 mmol/l had elevated in-hospital CRP (n=1107). Compared with patients with CRP levels within reference limit, elevated CRP was associated with older age (62 vs. 60, p<0.001), higher rates of diabetes (25.8% vs. 18.5%, p=0.002), renal failure (6.4% vs. 2.1%, p<0.001) and Killip class >1 at presentation (22.5% vs. 12.3%, p<0.001), as well as lower EF (44% vs. 48%, p<0.001) and lower haemoglobin on admission (13.9 g/dl vs. 14.2 g/dl, p<0.001). Crude mortality rates were increased in patients with CRP ≥5mg/l at both 30 days (6.0% vs. 2.4%, p=0.003) and 1 year (13.2% vs. 6.3%, p<0.001) (Figure). After adjusting for the observed baseline differences, CRP ≥5mg/l remained an independent predictor of mortality at 1 year (HR 1.691, 95% CI: 1.050–2.724, p=0.03), but not at 30 days (HR 1.690, 95% CI: 0.859–3.324, p=0.13). Conclusion In primary PCI-treated patients with residual cholesterol risk, elevated in-hospital CRP was independently associated with 1-year mortality. Our findings may thus suggest a potential window of opportunity, for anti-inflammatory therapies to improve outcomes beyond the acute phase. Figure 1 Funding Acknowledgement Type of funding source: None

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Evaluation of the relationship between anti-inflammatory cytokines and adverse cardiac remodeling after myocardial infarction

Kardiologiia ◽

10.18087/cardio.2021.10.n1749 ◽

2021 ◽

Vol 61 (10) ◽

pp. 61-70

Author(s):

Eyyupkoca Ferhat ◽

Ercan Karabekir ◽

Karakus Gultekin ◽

Karayigit Orhan ◽

Yildirim Onur ◽

...

Keyword(s):

Myocardial Infarction ◽

Inflammatory Cytokines ◽

Cardiac Remodeling ◽

Left Ventricular ◽

Magnetic Resonance Images ◽

Reverse Remodeling ◽

St Segment Elevation ◽

Systolic Volume ◽

End Diastolic Volume ◽

Anti Inflammatory

Aim To clarify the role of interleukin (IL) – 10 and members of its subfamily (IL-19 and IL-26) in cardiac remodeling during the post-myocardial infarction (MI) period.Material and methods A total of 45 patients with ST-segment elevation MI were enrolled. Serum cytokine concentrations were measured at the first day and 14 days post-MI. Left ventricular (LV) reverse remodeling (RR) was defined as the reduction of LV end-diastolic volume or LV end-systolic volume by ≥ 12 % in cardiac magnetic resonance images at 6‑mo follow-up. A 12 % increase was defined as adverse remodeling (AR).Results The post-MI first-day median IL-10 (9.7 pg / ml vs. 17.6 pg / ml, p<0.001), median IL-19 (28.7 pg / ml vs. 36.9 pg / ml, p<0.001), and median IL-26 (47.8 pg / ml vs. 90.7 pg / ml, p<0.001) were lower in the RR group compared to the AR group. There was a significant decrease in the concentration of anti-inflammatory cytokines in the AR group from the first to the 14 days post-MI. However, no significant change was observed in the RR group. Regression analysis revealed that a low IL-10 concentration on the post-MI first day was related to RR (OR=0.76, p=0.035). A 1 % increase in change of IL-10 concentration increased the probability of RR by 1.07 times.Conclusion The concentrations of cytokines were higher in the AR group, but this elevation was not sustained and significantly decreased for the 14 days post-MI. In the RR group, the concentrations of cytokines did not change and stable for the 14 days post-MI. As a reflection of this findings, stable IL-10 concentration may play a role the improvement of cardiac functions.

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The impact of anti-inflammatory cytokines on the pancreatic β-cell

Islets ◽

10.4161/19382014.2014.950547 ◽

2014 ◽

Vol 6 (3) ◽

pp. e950547 ◽

Cited By ~ 38

Author(s):

M A Russell ◽

N G Morgan

Keyword(s):

Inflammatory Cytokines ◽

Pancreatic Β Cell ◽

Β Cell ◽

Anti Inflammatory ◽

The Impact

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The Impact of Mild Heat Stress During Prolonged Running On Gastrointestinal Integrity, Gastrointestinal Symptoms, Systemic Endotoxin and Cytokine Profiles

International Journal of Sports Medicine ◽

10.1055/s-0043-122742 ◽

2018 ◽

Vol 39 (04) ◽

pp. 255-263 ◽

Cited By ~ 18

Author(s):

Rhiannon Snipe ◽

Anthony Khoo ◽

Cecilia Kitic ◽

Peter Gibson ◽

Ricardo Costa

Keyword(s):

Small Intestine ◽

Heat Stress ◽

Inflammatory Cytokines ◽

Gastrointestinal Symptoms ◽

Ambient Conditions ◽

Fatty Acid Binding ◽

Post Exercise ◽

Cytokine Profiles ◽

Anti Inflammatory ◽

The Impact

AbstractThe study aimed to determine the effects of mild exertional heat stress on intestinal injury, permeability, gastrointestinal symptoms, and systemic endotoxin and cytokine responses. Ten endurance runners completed 2 h of running at 60% V̇O2max in warm (WARM: 30°C) and temperate (TEMP: 22°C) ambient conditions. Rectal temperature (Tre) and gastrointestinal symptoms were recorded every 10 min during exercise. Blood samples were collected pre- and post-exercise, and during recovery to determine plasma intestinal fatty acid-binding protein (I-FABP) and cortisol concentrations, and systemic endotoxin and inflammatory cytokine profiles. Urinary lactulose:L-rhamnose ratio (L/R) was used to measure small intestine permeability. Compared with TEMP, WARM significantly increased Tre from 50 min onwards (38.1±0.3°C vs. 38.4±0.5°C, respectively; p<0.01), gastrointestinal symptoms (p=0.017), post-exercise plasma cortisol (26% vs. 59%, respectively; p<0.001) and I-FABP (127% vs. 184%, respectively; p<0.001) concentrations. Circulatory anti-endotoxin antibodies increased post-exercise (p<0.001) on WARM (20%) and TEMP (28%). No differences were observed for plasma endotoxin concentration (6% vs. 5% increase, respectively) or small intestine permeability (L/R 0.026±0.010 and 0.025±0.015, respectively). Both pro- and anti-inflammatory cytokines increased post-exercise, with inflammatory response cytokines TNF-α (p=0.015) and IL-8 (p=0.044), and compensatory anti-inflammatory cytokines IL-10 (p=0.065), and IL-1ra higher on WARM than TEMP. Findings suggest that exposure to warm ambient conditions during prolonged submaximal running induces transient intestinal epithelial injury, increases gastrointestinal symptoms, and promotes greater perturbations to the systemic cytokine profile compared to running in temperate conditions.

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Cannabis and Inflammation in HIV: A Review of Human and Animal Studies

Viruses ◽

10.3390/v13081521 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1521

Author(s):

Ronald J. Ellis ◽

Natalie Wilson ◽

Scott Peterson

Keyword(s):

Myocardial Infarction ◽

Adverse Effects ◽

Animal Studies ◽

Endocannabinoid System ◽

Cannabis Use ◽

Review Of The Literature ◽

Barrier Integrity ◽

Persistent Inflammation ◽

Anti Inflammatory ◽

The Impact

Persistent inflammation occurs in people with HIV (PWH) and has many downstream adverse effects including myocardial infarction, neurocognitive impairment and death. Because the proportion of people with HIV who use cannabis is high and cannabis may be anti-inflammatory, it is important to characterize the impact of cannabis use on inflammation specifically in PWH. We performed a selective, non-exhaustive review of the literature on the effects of cannabis on inflammation in PWH. Research in this area suggests that cannabinoids are anti-inflammatory in the setting of HIV. Anti-inflammatory actions are mediated in many cases through effects on the endocannabinoid system (ECS) in the gut, and through stabilization of gut–blood barrier integrity. Cannabidiol may be particularly important as an anti-inflammatory cannabinoid. Cannabis may provide a beneficial intervention to reduce morbidity related to inflammation in PWH.

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Assessment of regulatory/effector T cell balance along with pro/anti-inflammatory cytokines level in acute myocardial infarction

Indian Heart Journal ◽

10.1016/j.ihj.2014.10.048 ◽

2014 ◽

Vol 66 ◽

pp. S17

Author(s):

Saibal Mukhopadhyay ◽

Hariram Maharia ◽

Jamal Yusuf ◽

Vimal Mehta ◽

Vijay Trehan ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

T Cell ◽

Inflammatory Cytokines ◽

Effector T Cell ◽

Anti Inflammatory ◽

Cell Balance

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DIFFERENTIATION FACTORS OF M1 AND M2 SUBPOPULATIONS OF DECIDUAL MACROPHAGES IN PREGNANT WOMEN WITH PREECLAMPSIA, THEIR IMBALANCE AND WAYS TO CORRECT IT

Актуальні проблеми сучасної медицини Вісник Української медичної стоматологічної академії ◽

10.31718/2077-1096.20.3.14 ◽

2020 ◽

Vol 20 (3) ◽

pp. 14-19

Author(s):

V. L. Vashchenko ◽

V. K. Likhachov ◽

O. Ye. Akimov ◽

O. O. Taranovska

Keyword(s):

Pregnant Women ◽

Inflammatory Cytokines ◽

No Synthase ◽

Cervical Mucus ◽

Tnf Α ◽

Before And After ◽

Placental Site ◽

Anti Inflammatory ◽

The Difference ◽

The Impact

According to the literature, inappropriate polarization of decidual macrophages is associated with abnormal pregnancy conditions such as spontaneous abortion, premature childbirth, preeclampsia, foetal growth retardation, etc.; therefore, studying the relationship between subpopulations of decidual macrophages and factors promoting their production in women with preeclampsia is of great clinical relevance. The purpose of this study was to identify the features of differentiation in subpopulations M1 and M2 of decidual macrophages in pregnant women with preeclampsia and to assess the impact of factors promoting their induction. Materials and methods. The concentrations of pro- and anti-inflammatory cytokines (TNF-α, INF-γ, IL-10) and the activity of iNOS and arginase in cervical mucus in pregnant women with preeclampsia were studied in comparison with the corresponding indicators in healthy pregnant women, with subsequent comparison of these indicators with the number of decidual macrophages M1 and M2 in the placentas of the examined women. We determined the concentration of cytokines by using immunoassay. NO synthase activity was determined by the difference in nitrite concentration before and after cervical mucus incubation. The total arginase activity was assessed by the difference in the concentration of L-ornithine before and after incubation in phosphate buffered saline, which contained L-arginine. Immunohistochemical study of macrophages M1 and M2 in placental tissue was carried out in the pathomorphological laboratory "CSD Health Care" (Kiev). A total of 62 pregnant women were examined: the control group included 30 healthy pregnant women who did not have risk factors for preeclampsia and unimpaired circulation in the uterine spiral arteries in the area of the placental site at 18-20 + 6 weeks of gestation. The study group included 32 pregnant women at high risk to develop preeclampsia, with impaired circulation in the uterine spiral arteries in the area of the placental site at 18-20 + 6 weeks of gestation; 14 of them then developed preeclampsia. Results. In pregnant women with preeclampsia, the balance of pro- and anti-inflammatory cytokines is impaired in favour of TNF-α and INF-γ with a decrease in IL-10 content that results in an imbalance in the activity of enzymes regulating the L-arginine metabolism with the following increase in iNOS activity. The activity of arginine is significantly reduced. In the placentas of women with preeclampsia, the content of decidual macrophages M1 phenotype is 1.7 times higher than their number in healthy women, while the content of macrophages M2 phenotype, on the contrary, goes down in 1.5 times. The study has shown that the predominance of decidual M1 macrophages in women with preeclampsia occurs due to the stimulating effect of INF-γ and the activation of inducible NO-synthase. This imbalance of decidual macrophages in favour of the M1 subpopulation is likely to cause the progression of endothelial dysfunction, manifestation of preeclampsia, and dysfunction of the placenta in the second trimester and in the early phase of the third trimester of gestation.

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