scholarly journals Protective Effects of Methotrexate against Proatherosclerotic Cytokines: A Review of the Evidence

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Arduino A. Mangoni ◽  
Angelo Zinellu ◽  
Salvatore Sotgia ◽  
Ciriaco Carru ◽  
Matteo Piga ◽  
...  
Keyword(s):  
Rheumatic Disease ◽  
Vascular Inflammation ◽  
Interleukin 1 ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Disease States ◽  
Autoimmune Rheumatic Disease ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk ◽  
Meta Analyses

There is good epidemiological evidence that patients with autoimmune rheumatic disease states, particularly rheumatoid arthritis, have an increased risk of cardiovascular morbidity and mortality when compared to the general population. The presence of a chronic systemic proinflammatory state in this patient group disrupts the structural and functional integrity of the endothelium and the arterial wall, favouring the onset and progression of atherosclerosis. A significant role in the detrimental effects of inflammation on endothelial function and vascular homeostasis is played by specific proatherosclerotic cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). Recent systematic reviews and meta-analyses have shown that treatment with methotrexate, a first-line disease-modifying antirheumatic drug (DMARD), is associated with a significant reduction in atherosclerosis-mediated cardiovascular events, such as myocardial infarction and stroke, and mortality, when compared to other DMARDs. This suggests that methotrexate might exert specific protective effects against vascular inflammation and atherosclerosis in the context of autoimmune rheumatic disease. This review discusses the available evidence regarding the potential antiatherosclerotic effects of methotrexate through the inhibition of TNF-α, IL-1, and IL-6 and provides suggestions for future experimental and human studies addressing this issue.

scholarly journals The Relationship between Inflammatory Cytokines and Coagulopathy in Patients with COVID-19

2021 ◽  
Vol 10 (9) ◽  
pp. 2020
Author(s):  
Fariba Rad ◽  
Ali Dabbagh ◽  
Akbar Dorgalaleh ◽  
Arijit Biswas
Keyword(s):  
Inflammatory Cytokines ◽  
Interleukin 1 ◽  
Clinical Findings ◽  
Laboratory Findings ◽  
Necrosis Factor Alpha ◽  
Coagulation Parameters ◽  
Increased Risk ◽  
Cytokine Levels ◽  
Α Level ◽  
High Level

Coronavirus disease 2019 (COVID-19), with a broad range of clinical and laboratory findings, is currently the most prevalent medical challenge worldwide. In this disease, hypercoagulability and hyperinflammation, two common features, are accompanied by a higher rate of morbidity and mortality. We assessed the association between baseline inflammatory cytokine levels and coagulopathy and disease outcome in COVID-19. One hundred and thirty-seven consecutive patients hospitalized with COVID-19 were selected for the study. Baseline interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha (TNF-α) level were measured at time of admission. At the same time, baseline coagulation parameters were also assessed during the patient’s hospitalization. Clinical findings, including development of thrombosis and clinical outcome, were recorded prospectively. Out of 136 patients, 87 (~64%) had increased cytokine levels (one or more cytokines) or abnormal coagulation parameters. Among them, 58 (~67%) had only increased inflammatory cytokines, 12 (~14%) had only coagulation abnormalities, and 17 (19.5%) had concomitant abnormalities in both systems. It seems that a high level of inflammatory cytokines at admission points to an increased risk of developing coagulopathy, thrombotic events, even death, over the course of COVID-19. Early measurement of these cytokines, and timely co-administration of anti-inflammatories with anticoagulants could decrease thrombotic events and related fatal consequences.

Malignancy

2013 ◽  
pp. 172-176
Author(s):  
Jennifer Hamilton ◽  
Clive Kelly
Keyword(s):  
Rheumatic Disease ◽  
Evidence Base ◽  
Necrosis Factor Alpha ◽  
Relative Risks ◽  
Underlying Malignancy ◽  
Clinical Presentations ◽  
Increased Risk ◽  
Risk Of Malignancy ◽  
Musculoskeletal Manifestations ◽  
Factor Alpha

This chapter addresses the links between malignancy and rheumatic disease. It begins with a summary of rheumatological conditions associated with an increased risk of malignancy, and describes and discusses specific neoplasms associated with each rheumatic disorder. The present knowledge base is summarized in tabular form, describing the relative risks of different malignancies for each relevant rheumatic disease. The diseases featured include rheumatoid arthritis, primary Sjögren’s syndrome, scleroderma, dermatomyositis and systemic lupus. The next section reviews the drugs used in present rheumatological practice known to be associated with malignancy, describing the specific established risks linked to each of the following agents: azathioprine, cyclophosphamide, ciclosporin, anti-tumour necrosis factor alpha (TNFα‎‎) agents, and mycophenolate mofetil. The evidence base and strength of these associations are summarized. Finally we describe the musculoskeletal manifestations that arise as a consequence of underlying malignancy, considering bone pain, polymyalgia, arthropathy, and vasculitis as clinical presentations or complications of underlying neoplasia. This section also includes descriptions of less common rheumatic disorders that may also be associated with cancer, including erythema nodosum, Sweet’s syndrome, and pyoderma gangrenosum.

scholarly journals Impact of Coenzyme Q10 Administration on Lead Acetate-Induced Testicular Damage in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Manal El-khadragy ◽  
Wafa A. Al-Megrin ◽  
Norah A. AlSadhan ◽  
Dina M. Metwally ◽  
Rehab E. El-Hennamy ◽  
...  
Keyword(s):  
Coenzyme Q10 ◽  
Lead Acetate ◽  
Interleukin 1 ◽  
Tween 80 ◽  
Control Group ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Coq10 Supplementation ◽  
Induced Apoptosis ◽  
Testicular Injury

Exposure to lead (Pb) causes multiorgan dysfunction including reproductive impairments. Here, we examined the protective effects of coenzyme Q10 (CoQ10) administration on testicular injury induced by lead acetate (PbAc) exposure in rats. This study employed four experimental groups (n=7) that underwent seven days of treatment as follows: control group intraperitoneally (i.p.) treated with 0.1 ml of 0.9% NaCl containing 1% Tween 80 (v:v), CoQ10 group that was i.p. injected with 10 mg/kg CoQ10, PbAc group that was i.p. treated with PbAc (20 mg/kg), and PbAc+CoQ10 group that was i.p. injected with CoQ10 2 h after PbAc. PbAc injection resulted in increasing residual Pb levels in the testis and reducing testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Additionally, PbAc exposure resulted in significant oxidative damage to the tissues on the testes. PbAc raised the levels of prooxidants (malondialdehyde and nitric oxide) and reduced the amount of endogenous antioxidative proteins (glutathione and its derivative enzymes, catalase, and superoxide dismutase) available in the cell. Moreover, PbAc induced the inflammatory response as evidenced by the upregulation of inflammatory mediators (tumor necrosis factor-alpha and interleukin-1 beta). Further, PbAc treatment induced apoptosis in the testicular cells, as indicated by an increase in Bax and caspase 3 expression, and reduced Bcl2 expression. CoQ10 supplementation improved testicular function by inhibiting Pb accumulation, oxidative stress, inflammation, cell death, and histopathological changes following PbAc exposure. Our findings suggest that CoQ10 can act as a natural therapeutic agent to protect against the reproductive impairments associated with PbAc exposure.

scholarly journals Immunomodulating effect of fosfomycin on gut-derived sepsis caused by Pseudomonas aeruginosa in mice.

1997 ◽  
Vol 41 (2) ◽  
pp. 308-313 ◽  
Author(s):  
T Matsumoto ◽  
K Tateda ◽  
S Miyazaki ◽  
N Furuya ◽  
A Ohno ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Survival Rate ◽  
Protective Effect ◽  
Specific Activity ◽  
Bacterial Colonization ◽  
Interleukin 1 ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Bacterial Clearance ◽  
Necrosis Factor Alpha

We evaluated the protective effect of fosfomycin (FOM) and an enantiomer of fosfomycin [FOM (+); an isomer of FOM with no bactericidal activity] on murine gut-derived sepsis caused by Pseudomonas aeruginosa. Endogenous bacteremia was induced by administering cyclophosphamide (CY) and ampicillin to specific-pathogen-free mice fed P. aeruginosa. Treatment of mice with FOM at 250 mg/kg of body weight per day twice a day after the second CY administration significantly increased the survival rate compared to that for control mice treated with saline. Treatment with FOM (+) at 20 and 100 mg/kg also significantly increased the survival rate (from 30% for control mice to 80% for treated mice). The bacterial counts in the liver and blood were both significantly lower in FOM(+)-treated mice in comparison with those in liver and blood of saline-treated control mice. FOM(+) administration affected neither the bacterial colonization in the intestinal tract nor the leukocyte counts in the peripheral blood of the mice. After intravascular inoculation of P. aeruginosa, treatment of mice with FOM (+) did not enhance bacterial clearance from the blood of mice pretreated or not enhance bacterial clearance from the blood of mice pretreated or not pretreated with CY, FOM(+) significantly suppressed tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 levels in the serum of mice after gut-derived sepsis. These results indicate that both FOM and FOM(+) have protective effects against P. aeruginosa bacteremia, despite a lack of specific activity of FOM(+), and suggest that FOM may possess immunomodulating activity and that it induces a protective effect. The protective mechanism is speculated to be that FOM modulates the vivo production of inflammatory cytokines.

Effect of heat-killed Enterococcus faecalis EF-2001 on ethanol-induced acute gastric injury in mice: Protective effect of EF-2001 on acute gastric ulcer

2020 ◽  
Vol 39 (5) ◽  
pp. 721-733 ◽  
Author(s):  
D-B Jeon ◽  
H-G Shin ◽  
B-W Lee ◽  
S-H Jeong ◽  
J-H Kim ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Enterococcus Faecalis ◽  
Interleukin 1 ◽  
Mucosal Injury ◽  
Underlying Mechanism ◽  
Gastric Injury ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Mitogen Activated Protein ◽  
Consequent Reduction

Enterococcus faecalis is a facultative anaerobic gram-positive commensal bacterium common in the gastrointestinal tract of animals and humans. This study aimed to investigate the protective effects of heat-killed E. faecalis EF-2001 (EF-2001) on acute gastric ulcer using a murine model of ethanol (EtOH)-induced acute gastric injury. EF-2001 (20, 40, and 80 mg/kg/day) was administered by oral gavage for 5 days before EtOH treatment (10 mL/kg body weight). EF-2001 effectively attenuated EtOH-induced gastric mucosal injury with reduced gastric mucosal ulcer and histological damage score. Pretreatment of EF-2001 markedly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs; ERK1/2, JNK, and p38MAPK). In addition, EF-2001 significantly inhibited phosphorylation of nuclear factor kappa B (NF-κB) and subsequently suppressed the upregulation of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in gastric tissues. Taken together, these results suggest that EF-2001 exerts a gastroprotective effect against acute gastric injury, and the underlying mechanism might be associated with the suppression of MAPKs and NF-κB signaling and consequent reduction of pro-inflammatory mediators or cytokines.

scholarly journals Therapeutic Effects of Chinese Medicine Herb Pair, Huzhang and Guizhi, on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats Revealed by Anti-Inflammatory Assessments and NMR-Based Metabonomics

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Bin Han ◽  
Huizhu Huang ◽  
Zhong Li ◽  
Mengjuan Gong ◽  
Wan Shi ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Gouty Arthritis ◽  
Pathological Process ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Monosodium Urate ◽  
Necrosis Factor Alpha ◽  
Gut Microbe ◽  
Urate Crystal ◽  
Factor Alpha

The present study was undertaken to evaluate the therapeutic effects of Huzhang-Guizhi herb pair (HG), firstly included in Hu-Zhang Power documented in Taiping Shenghui Fang, on monosodium urate (MSU) crystals-induced gouty arthritis in rats. We found that pretreatment with HG in rats with gouty arthritis could significantly attenuate the ankle joint swelling, and this beneficial antigout effect might be mediated, at least in part, by inhibiting tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) production in synovial fluid as well as nuclear transcription factor-κB p65 (NF-κB p65) protein expression in synovial tissue. Moreover, metabonomic analysis demonstrated that 5 and 6 potential biomarkers associated with gouty arthritis in plasma and urine, respectively, which were mainly involved in energy metabolism, amino acid metabolism, and gut microbe metabolism, were identified. HG could reverse the pathological process of MSU-induced gouty arthritis through regulating the disturbed metabolic pathways. These results provided important mechanistic insights into the protective effects of HG against MSU-induced gouty arthritis in rats.

Evidence for activation of endothelium and monocytes in hypertensive rats

1996 ◽  
Vol 270 (6) ◽  
pp. H2125-H2131 ◽  
Author(s):  
Y. Liu ◽  
T. Liu ◽  
R. M. McCarron ◽  
M. Spatz ◽  
G. Feuerstein ◽  
...  
Keyword(s):  
Carotid Arteries ◽  
Interleukin 1 ◽  
Intercellular Adhesion Molecule ◽  
Blood Monocytes ◽  
Hypertensive Rats ◽  
Internal Elastic Lamina ◽  
Rat Strains ◽  
Necrosis Factor Alpha ◽  
Increased Risk ◽  
Wistar Kyoto

We have proposed that an interaction between perivascular macrophages and endothelium via cytokines could underlie the increased risk of stroke in hypertension. Therefore, the activation of monocytes, the endothelial expression of intercellular adhesion molecule-1 (ICAM-1), and the numbers of monocytes/macrophages in carotid arteries, as well as the cytokine production in carotid tissue, of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto and Sprague-Dawley rats were studied. The total number of blood monocytes (890 +/- 153 cells/mm3, n = 10) and the number of activated (nitro blue tetrazolium-positive) monocytes (220 +/- 51 cells/mm3, n = 10) were significantly greater (P < 0.05) in SHR than in WKY rats (440 +/- 81 and 40 +/- 16 cells/mm3, respectively, n = 10). Patchy endothelial expression of ICAM-1 was found in 77 +/- 9% of carotid sections from stroke-prone SHR (SHR-SP, n = 5) and in 75 +/- 7% of the sections from SHR (n = 7) but in none of the sections from the two normotensive rat strains (n = 7). The number of endothelium-attached monocytes/macrophages per millimeter of internal elastic lamina was significantly greater in SHR-SP than in SHR [5.1 +/- 0.7 (n = 4) and 3.3 +/- 0.3 (n = 6), P < 0.05], whereas no monocytes were found around the endothelium in either of the normotensive rat strains (n = 7 in each group). Incubation of the carotid arteries with lipopolysaccharide (30-300 ng/ml) induced a concentration-dependent expression of mRNAs for interleukin-1 beta and release of tumor necrosis factor-alpha to a significantly greater degree in the SHR than in the Wistar-Kyoto rats. The results demonstrate that hypertension is associated with activation of monocytes and endothelium and an increased endothelial adhesion and subendothelial accumulation of monocytes/macrophages and with an increased vascular capacity to produce cytokines.

scholarly journals Risk of progression of interstitial pneumonia with autoimmune features to a systemic autoimmune rheumatic disease

Rheumatology ◽  
2019 ◽  
Vol 59 (6) ◽  
pp. 1233-1240 ◽  
Author(s):  
Michail K Alevizos ◽  
Jon T Giles ◽  
Nina M Patel ◽  
Elana J Bernstein
Keyword(s):  
Rheumatic Disease ◽  
Interstitial Pneumonia ◽  
Smoking Status ◽  
Medical Center ◽  
Columbia University ◽  
Autoimmune Rheumatic Disease ◽  
Increased Risk ◽  
Systemic Autoimmune Rheumatic Disease ◽  
Risk Of Progression

Abstract Objective The aim of this study was to determine the risk of developing a systemic autoimmune rheumatic disease (ARD) after an initial diagnosis of interstitial pneumonia with autoimmune features (IPAF). Methods We performed a retrospective cohort study of patients with interstitial lung disease (ILD) who were evaluated at Columbia University Irving Medical Center from 2009 to 2017. We divided patients with idiopathic ILD into two groups: those who met IPAF criteria and those who did not meet IPAF criteria at initial ILD diagnosis. We examined the association between IPAF and diagnosis of ARD during the follow-up period using a multivariable-adjusted logistic regression model. Results Of the 697 patients with ILD who were screened, 174 met inclusion criteria (50 met IPAF criteria and 124 did not). During a median follow-up period of 5.2 years, 16% (8/50) of subjects with IPAF were diagnosed with an ARD compared with 1.6% (2/124) of subjects without IPAF (P = 0.001). Adjusting for age, sex, smoking status and use of immunosuppressive therapy, the odds of progressing to an ARD were 14 times higher in subjects with IPAF than in those without IPAF (odds ratio 14.18, 95% CI 1.44–138.95, P = 0.02). Conclusion The presence of IPAF confers an increased risk of developing an ARD. Patients with IPAF should therefore be followed closely for the development of an ARD.

scholarly journals Protective Effects of Carvedilol and Vitamin C against Azithromycin-Induced Cardiotoxicity in Rats via Decreasing ROS, IL1-β, and TNF-αProduction and Inhibiting NF-κB and Caspase-3 Expression

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Nagla A. El-Shitany ◽  
Karema El-Desoky
Keyword(s):  
Lactate Dehydrogenase ◽  
Vitamin C ◽  
Glutathione Peroxidase ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Interleukin 1 ◽  
Protective Effects ◽  
Histopathological Changes ◽  
Cardiovascular Risks ◽  
Necrosis Factor Alpha

The Food and Drug Administration recently warned of the fatal cardiovascular risks of azithromycin in humans. In addition, a recently published study documented azithromycin-induced cardiotoxicity in rats. This study aimed to justify the exact cardiovascular events accompanying azithromycin administration in rats, focusing on electrocardiographic, biochemical, and histopathological changes. In addition, the underlying mechanisms were studied regarding reactive oxygen species production, cytokine release, and apoptotic cell-death. Finally, the supposed protective effects of both carvedilol and vitamin C were assessed. Four groups of rats were used: (1) control, (2) azithromycin, (3) azithromycin + carvedilol, and (4) azithromycin + vitamin C. Azithromycin resulted in marked atrophy of cardiac muscle fibers and electrocardiographic segment alteration. It increased the heart rate, lactate dehydrogenase, creatine phosphokinase, malondialdehyde, nitric oxide, interleukin-1 beta (IL1-β), tumor necrosis factor alpha (TNF-α), nuclear factor kappa beta (NF-κB), and caspase-3. It decreased reduced glutathione, glutathione peroxidase, and superoxide dismutase. Carvedilol and vitamin C prevented most of the azithromycin-induced electrocardiographic and histopathological changes. Carvedilol and vitamin C decreased lactate dehydrogenase, malondialdehyde, IL1-β, TNF-α, NF-κB, and caspase-3. Both agents increased glutathione peroxidase. This study shows that both carvedilol and vitamin C protect against azithromycin-induced cardiotoxicity through antioxidant, immunomodulatory, and antiapoptotic mechanisms.

scholarly journals Extracts from Fermented Black Garlic Exhibit a Hepatoprotective Effect on Acute Hepatic Injury

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1112 ◽  
Author(s):  
Jen-Chieh Tsai ◽  
Yi-An Chen ◽  
Jung-Tsung Wu ◽  
Kuan-Chen Cheng ◽  
Ping-Shan Lai ◽  
...  
Keyword(s):  
Hepatic Injury ◽  
Interleukin 1 ◽  
Water Layer ◽  
Hepatoprotective Effect ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Acute Hepatic Injury ◽  
Factor Alpha ◽  
Anti Inflammatory

The mechanism of hepatoprotective compounds is usually related to its antioxidant or anti-inflammatory effects. Black garlic is produced from garlic by heat treatment and its anti-inflammatory activity has been previously reported. Therefore, the aim of this study was to investigate the hepatoprotective effect of five different extracts of black garlic against carbon tetrachloride (CCl4)-induced acute hepatic injury (AHI). In this study, mice in the control, CCl4, silymarin, and black garlic groups were orally administered distilled water, silymarin, and different fraction extracts of black garlic, respectively, after CCl4 was injected intraperitoneally to induce AHI. The results revealed that the n-butanol layer extract (BA) and water layer extract (WS) demonstrated a hepatoprotective effect by reducing the levels of alanine aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and hepatic malondialdehyde (MDA). Furthermore, the BA and WS fractions of black garlic extract increased the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd), tumor necrosis factor alpha (TNF-α), and the interleukin-1 (IL-1β) level in liver. It was concluded that black garlic exhibited significant protective effects on CCl4-induced acute hepatic injury.

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