Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: Rationale and Design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS)

The role of inflammation in atherosclerosis has been recognized several decades ago and existing treatments provide benefits in part through non-specific anti-inflammatory actions. Compared with other cytokines, interleukin-1β (IL-1β) is associated with acute and chronic inflammation. Anti-inflammatory therapy with canakinumab targeting the IL-1β innate immunity pathway could significantly reduce the rate of recurrent cardiovascular events than placebo. The results of CANTOS suggested an important role of IL-1β in atherosclerosis. However, there are numerous mechanisms that are to be clarified. We herein discussed the important immunomodulatory effect IL-1β exerts on atherosclerosis and the potential mechanisms underlying it. We also reviewed bench-to-bedside clinical translation of IL-1β neutralizing strategies associated with the use of IL-1β blockade in patients with atherosclerosis.

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Nonsteroid anti-inflammatory drugs (NSAID) and risk of cardiovascular events. Literature review and clinical implications

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2014.58 ◽

2015 ◽

Vol 82 (3) ◽

Cited By ~ 1

Author(s):

Pier Luigi Temporelli ◽

Giovanni Battista Zito ◽

Roberto Franco Pedretti ◽

Francesco Iachini Belisarii ◽

Giuseppe Putortì ◽

...

Keyword(s):

Chronic Pain ◽

Cardiovascular Events ◽

Large Body ◽

Cyclooxygenase Inhibitors ◽

Current Status ◽

Analgesic Drugs ◽

Drug Agency ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Artery Disease

Non steroid anti-inflammatory drugs (NSAIDs) are largely used for treatment of acute and chronic pain, even for long periods of time (months or years). While it is known that their use is frequently associated with gastrointestinal damage, including major bleedings from peptic ulcer, the risk of cardiovascular events related to NSAID has received much less attention. However, there is a large body of evidence showing that NSAIDs (both “traditional”, such as diclofenac or indobufen, and selective cyclooxygenase inhibitors, COX-2) are associated with a significant increase of risk of cardiovascular events, both fatal and nonfatal. Consequently, several options have been proposed for the treatment of pain, including the use of analgesic drugs with different mechanisms of action, such as the opiates. Of interest, the Italian Drug Agency (AIFA) published a few years ago a warning (Nota 66) on the careful prescription of NSAIDs in patients with overt heart disease, such as coronary artery disease and heart failure. Aim of this paper is to present the current status of knowledge on the proper use of NSAIDs and other analgesic drugs in the management of acute and chronic pain.

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Establishment of an interleukin-1β-induced inflammation-activated endothelial cell-smooth muscle cell-mononuclear cell co-culture model and evaluation of the anti-inflammatory effects of tanshinone IIA on atherosclerosis

Molecular Medicine Reports ◽

10.3892/mmr.2015.3668 ◽

2015 ◽

Vol 12 (2) ◽

pp. 1665-1676 ◽

Cited By ~ 14

Author(s):

YUJIE LI ◽

YAN GUO ◽

YING CHEN ◽

YAJIE WANG ◽

YUN YOU ◽

...

Keyword(s):

Smooth Muscle ◽

Endothelial Cell ◽

Smooth Muscle Cell ◽

Mononuclear Cell ◽

Muscle Cell ◽

Tanshinone Iia ◽

Interleukin 1Β ◽

Culture Model ◽

Anti Inflammatory

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Effect of colchicine, methotrexate, and hydroxychloroquine therapy on cardiovascular outcomes in patients with calcium pyrophosphate crystal deposition disease

Modern Rheumatology Journal ◽

10.14412/1996-7012-2021-6-76-83 ◽

2021 ◽

Vol 15 (6) ◽

pp. 76-83

Author(s):

M. S. Eliseev ◽

E. V. Cheremushkina ◽

O. V. Zhelyabina ◽

M. N. Chikina ◽

A. A. Kapitonova ◽

...

Keyword(s):

Cardiovascular Events ◽

Serum Uric Acid Level ◽

Calcium Pyrophosphate ◽

Chronic Arthritis ◽

Cardiovascular Outcomes ◽

Crystal Deposition ◽

Crystal Deposition Disease ◽

Deposition Disease ◽

History Of ◽

Anti Inflammatory

Anti-inflammatory therapy, such as colchicine (COL), has been suggested to affect the incidence of cardiovascular events in patients with calcium pyrophosphate crystal deposition disease (CPPD).Objective: to study the effect of anti-inflammatory therapy with COL, hydroxychloroquine (HC), and methotrexate (MT) on cardiovascular outcomes in patients with CPPD.Patients and methods. The study included 305 patients with CPPD, the majority (62.30%) were women. The average follow-up period was 3.9±2.7 years. Among factors influencing cardiovascular outcome were considered: gender; age; smoking; alcohol intake >20 conventional doses per week; arterial hypertension; a history of cardiovascular diseases (CVD), in particular ischemic heart disease, acute myocardial infarction, acute cerebrovascular accident, chronic heart failure >III stage according to NYHA, as well as type 2 diabetes mellitus (DM); body mass index >25 kg/m2 and >30 kg/m2; cholesterol level (CHOL) >5.1 mmol/l; glomerular filtration rate (GFR) < 60 ml/min/1.73 m2; serum uric acid level >360 μmol/l; hypercalcemia (serum calcium level >2.62 mmol/L); CRP level >2 mg/l; the presence of hyperparathyroidism (parathyroid hormone level >65 pg/ml); CPPD phenotypes (asymptomatic, osteoarthritis with calcium pyrophosphate crystals, chronic arthritis, acute arthritis); intake of COL, HC, MT, glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs).Results and discussion. 264 patients were under dynamic observation. Any of the studied cardiovascular events were registered in 79 (29.9%) patients. During the observation period, 46 (17.4%) patients died, in 76.1% of cases the cause of death was CVD. Death from other causes was diagnosed in 11 (23.9%) patients. Non-fatal cardiovascular events were reported in 44 (16.7%) cases. The risk of cardiovascular events was higher in patients over 65 years of age (odds ratio, OR 5.97; 95% confidence interval, CI 3.33–10.71), with serum cholesterol levels ≥5.1 mmol/L (OR 1,95; 95% CI 1.04–3.65), GFR <60 ml/min/1.73 m2 (OR 2.78; 95% CI 1.32–5.56), history of CVD (OR 2,32; 95% CI 1.22–4.44). COL therapy reduced the risk of cardiovascular events (OR 0.20; 95% CI 0.11–0.39).Conclusion. Poor CVD outcomes in CPPD are associated with age, hypercholesterolemia, chronic kidney disease, and a history of CVD. The use of COL, in contrast to MT and HC, was accompanied by a decrease in cardiovascular risk.

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Influence of Cannabinoid on Interleukin-1β Treated Cartilage: An In Vitro Study

Foot & Ankle Orthopaedics ◽

10.1177/2473011420s00436 ◽

2020 ◽

Vol 5 (4) ◽

pp. 2473011420S0043

Author(s):

Jiangyinzi Shang ◽

Yuning Hu ◽

Peter Alexander ◽

MaCalus V. Hogan ◽

Hang Lin ◽

...

Keyword(s):

Real Time ◽

Joint Damage ◽

In Vitro Study ◽

Interleukin 1Β ◽

Human Chondrocytes ◽

High Dose ◽

Engineer Cartilage ◽

Anti Inflammatory ◽

Win 55

Category: Basic Sciences/Biologics Introduction/Purpose: Cannabinoids have been reported to possess the analgesic, immunomodulatory and anti-inflammatory properties. Recent studied further shown that cannabinoids attenuated joint damage in animal models of arthritis. However, the underlying mechanism has been completely understood. Interleukin-1β (IL-1β), a proinflammatory cytokine that can result in the degradation of cartilage, is associated with the pathogenesis of osteoarthritis. In this study, we hypothesize that cannabinoid can mitigate the detrimental effect of IL-1β on cartilage, thus reduce the progression of osteoarthritis. To test the hypothesis, we insulted human chondrocyte-derived cartilage with IL-1 β for 48 hours and then applied a synthetic cannabinoid agonist, Win- 55,212-2(Win-55), into the culture. The tissue phenotypes were assessed by real time polymerase chain reaction (PCR), histology and immunostaining. Methods: With the approval from CORID, human chondrocytes were isolated from healthy articular cartilage. P2 cells were used. MTS assay were employed to test the half-maximal (50%) inhibitory concentration (IC50). To generate cartilage in vitro, chondrocytes were pelleted and subjected to 14 days chondrogenic culture. The engineered cartilages were stimulated with 10 ng/ml IL-1β for 48 hours and then treated with different concentration of Win-55 (0.01, 0.1, or 1 µM) for another 48 hours. The tissue phenotype was assessed by glycosaminoglycan (GAG) assay, real-time PCR and histology. Results: We tested 10 doses, from 0.001µM up to 10 µM, and determined that the IC 50 of Win-55 on human chondrocytes for 2 days was ˜ 2 µM. Interestingly, this dose is significantly lower than the doses reported in similar studies. As shown in Figure 1, treatment with 2µM Win-55 causes the complete loss of GAG from engineer cartilage. In a relatively safe dose (<=1 µM), we did not observe obvious changes in all tested genes after the treatments of Win-55 (Figure 2). Conclusion: High dose of Win-55 may directly cause the degeneration of cartilage, while low dose of Win-55 doesn’t show beneficial influence on the phenotype of IL1-β-insulted cartilage. The reported anti-inflammatory effect of Win 55 on chondrocytes may due to the cytotoxicity or global inhibition of high dose Win 55 on cell activities. Therefore, if cannabinoid can be used to treat OA requires further investigation.

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