Interleukin 37 reverses the metabolic cost of inflammation, increases oxidative respiration, and improves exercise tolerance.

IL-1 family member interleukin 37 (IL-37) has broad antiinflammatory properties and functions as a natural suppressor of innate inflammation. In this study, we demonstrate that treatment with recombinant human IL-37 reverses the decrease in exercise performance observed during systemic inflammation. This effect was associated with a decrease in the levels of plasma and muscle cytokines, comparable in extent to that obtained upon IL-1 receptor blockade. Exogenous administration of IL-37 to healthy mice, not subjected to an inflammatory challenge, also improved exercise performance by 82% compared with vehicle-treated mice (P = 0.01). Treatment with eight daily doses of IL-37 resulted in a further 326% increase in endurance running time compared with the performance level of mice receiving vehicle (P = 0.001). These properties required the engagement of the IL-1 decoy receptor 8 (IL-1R8) and the activation of AMP-activated protein kinase (AMPK), because both inhibition of AMPK and IL-1R8 deficiency abrogated the positive effects of IL-37 on exercise performance. Mechanistically, treatment with IL-37 induced marked metabolic changes with higher levels of muscle AMPK, greater rates of oxygen consumption, and increased oxidative phosphorylation. Metabolomic analyses of plasma and muscles of mice treated with IL-37 revealed an increase in AMP/ATP ratio, reduced levels of proinflammatory mediator succinate and oxidative stress-related metabolites, as well as changes in amino acid and purine metabolism. These effects of IL-37 to limit the metabolic costs of chronic inflammation and to foster exercise tolerance provide a rationale for therapeutic use of IL-37 in the treatment of inflammation-mediated fatigue.

Is evaluation of complex polymorphism helpful in the assessment of prognosis after percutaneous coronary intervention. A prospective study.

BACKGROUND: Coronary artery disease (CAD) is a complex disorder accounting for the majority of cardiovascular deaths and morbidity. It is believed that genetic factors explain part of the excessive risk of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI). AIM: To evaluate the influence on long-term prognosis of some genetic polymorphisms affecting renin-angiotensin system, inflammatory response, beta-2 adrenergic receptor, nitric oxide and platelets activity in patients with stable CAD undergoing routine PCI. METHODS: The study population consisted of 110 consecutive male patients with stable angina undergoing elective, single-vessel PCI. Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism-based techniques. Follow-up data were obtained by postal questionnaires regarding survival, myocardial infarction and revascularisation procedures. The control group consisted of 78 healthy males. RESULTS: Compared to controls, the distribution of polymorphisms among patients differed with regard to interleukin-1 receptor antagonist and CD14 variants. Patients who had PCI during follow-up in comparison with the remaining patients had a similar genetic profile, but higher triglycerides (1.9 vs 1.5 mmol/L, p = 0.01) and atherogenic index (3.8% vs 3.1%, p = 0.03) and lower percentage of HDL (21.8% vs 25.0%, p = 0.02). Among subjects with any revascularisation procedures, a similar clinical profile was observed. However, they differed from those without any procedures regarding the distribution of angiotensinogen M235T variants (MM%/TM%/TT%) 28%/64%/8% vs 19%/50%/31%, p = 0.048. Stratification for myocardial infarction showed association with selectin E variants (AA%/AC%/CC%) 57.1%/28.6%/14.3% vs 78.8%/21.2%/0%, p = 0.055 and higher triglycerides (2.11 vs 1.57 mmol/L, p = 0.055). CONCLUSIONS: Although we cannot exclude the role of polymorphism in angiotensinogen and selectin E genes, the prognosis of patients post-PCI in our study was mainly influenced by risk factors related to lipid metabolisms.