The varying faces of IL-6: From cardiac protection to cardiac failure

Abstract

IL6 is a pleiotropic cytokine that is made in response to perturbations in homeostasis. IL6 becomes elevated in the acute response to host injury and can activate immune cells, direct immune cell trafficking, signal protective responses in local tissue, initial the acute phase response or initiate wound healing. In the short term this proinflammatory response is protective and limits host damage. It is when this acute response remains chronically activated that IL6 becomes pathogenic to the host. Chronically elevated IL6 levels lead to chronic inflammation and fibrotic disorders. The heart is a tissue where this temporal regulation of IL6 is very apparent. Studies from myocardial infarction show how short-term IL6 signaling can protect and preserve the heart tissue in response to acute damage, where long term IL6 signaling or an over-production of IL6R protein plays a causal role in cardiovascular disease. Thus, IL6 can be both protective and pathogenic, depending on the kinetics of the host response.

Sex-specific differences in risk factors for sarcopenia amongst community-dwelling older adults

“…Further, we failed to detect significant correlations between ABSI which is representative of adiposity and serum IL-6 levels. The longitudinal tracking of inflammatory markers with sarcopenic status will be especially pertinent given the pleiotropic nature of IL-6 (Fontes et al 2015), along with its recognition as a myokine, being secreted by skeletal muscle with potential benefits that include improved skeletal muscle glucose uptake and insulin sensitivity in response to exercise (Pal et al 2014). Our study's strengths include a well-characterized cohort of older adults with complete clinical, imaging and biochemical parameters, incorporating functional performance measures beyond mere muscle mass in Table 4 Gender-specific biochemical parameters associated with sarcopenia-female (N=137) and male (N=63) FBC full blood count, CRP C-reactive protein, Hb haemoglobin, HDL high density lipoprotein, IGF-1 insulin-like growth factor-1, IL-6 interleukin-6, LDL low density lipoprotein, TG triglyceride, WBC white blood cell count Model 1: R 2 =16.7 %; model 2: R 2 =14.4 % defining sarcopenia, thereby according due recognition that mere measurement of quantitative muscle mass may not accurately reflect important changes impacting muscle performance.…”

Novel heart failure biomarkers: why do we fail to exploit their potential?

“…Inflammation is an important process in HF, and substances related to inflammation, such as interleukin-6 (IL-6), could serve as HF biomarkers [5,110]. In the acute phase after myocardial infarction, IL-6 elevation is beneficial because it induces anti-apoptotic mechanisms in cardiomyocytes, and it is believed to limit infarct size [110].…”

“…In the acute phase after myocardial infarction, IL-6 elevation is beneficial because it induces anti-apoptotic mechanisms in cardiomyocytes, and it is believed to limit infarct size [110]. However, IL-6 can also alter Ca 2þ handling, and long-term IL-6 signaling is associated with depressed cardiomyocyte function, myocardial hypertrophy, and decreased contractility [110,111]. Limiting the long-term effects of IL-6 on the failing heart by blockade of the IL-6 receptor could therefore result in improved cardiac function, and the IL-6 receptor has been identified as an HF treatment target [112].…”

Measuring myokines with cardiovascular functions: pre-analytical variables affecting the analytical output

“…It is independent of TNF-α (83) and it is not associated with myocyte damage (76) but it drives muscle regeneration and recovery from atrophy (84,85). In AMI, short-term IL-6 signaling has protective effects, while long-term signaling, or IL-6R over-expression, perpetuates the damage (68).…”

“…Although synthesized by all cell types, main sources are: hepatocytes, T-cells, macrophages, smooth and SKM cells. It regulates acute-phase response, inflammation, and hematopoiesis (68). IL-6 receptor (IL-6R) is expressed by a limited number of cell types [e.g., bone cells, and myocytes (69)] while the co-receptor gp130 is ubiquitously expressed and is activated by all the IL-6 family members [leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), oncostatin M (OSM), IL-11, ciliary neurotrophic factor (CNTF)] (70).…”