IL-6 family cytokines as potential therapeutic strategies to treat metabolic diseases

Zhao, Jingjing; Turpin-Nolan, Sarah M.; Febbraio, Mark A.

doi:10.1016/j.cyto.2021.155549

Cited by 9 publications

(3 citation statements)

References 102 publications

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“…Careful consideration of specific pre-clinical models, stage of disease, treatment duration, and muscle heterogeneity should be considered when constructing experimental designs with direct assessments of muscle force generating capacities complemented with whole body functional assessments. The divergent responses of cytokines between studies investigating ALY688 in mdx mouse models of DMD, despite a consistent response of lower fibrosis, may be consistent with prior reports that show specific cytokines can be both pro-or anti-inflammatory depending on specific contexts [119] which underscores the complexities of cytokines in remodeling dystrophic muscle during disease progression. Furthermore, resolving the apparent complexities in the inflammatory and metabolic responses to these approaches will give new insight into the fundamental mechanisms by which adiponectin receptors modify disease development in pre-clinical models in addition to guiding translational efforts towards clinical trials.…”

Section: Discussionsupporting

confidence: 85%

Recent Advances in Pre-clinical Development of Adiponectin Receptor Agonist Therapies for Duchenne Muscular Dystrophy

Gandhi,

Sweeney,

Perry

2024

Preprint

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Duchenne muscular dystrophy (DMD) is caused by genetic mutations in the cytoskeletal-sarcolemmal anchor protein dystrophin. Repeated cycles of sarcolemmal tearing and repair lead to a variety of secondary cellular and physiological stressors that are thought to contribute to weakness, atrophy, and fibrosis. Collectively, these stressors can contribute to a pro-inflammatory milieu in locomotor, cardiac, and respiratory muscles. Given the many unwanted side effects that accompany current anti-inflammatory steroid-based approaches for treating DMD (e.g., glucocorticoids), there is a need to develop new therapies that address inflammation and other cellular dysfunctions. Adiponectin receptor (AdipoR) agonists, which stimulate AdipoR1 and R2 isoforms on various cell types, have emerged as therapeutic candidates for DMD due to their anti-inflammatory, anti-fibrotic, and pro-myogenic properties in pre-clinical human and rodent DMD models. Although these molecules represent a new direction for therapeutic intervention, the mechanisms through which they elicit their beneficial effects are not yet fully understood, and DMD-specific data is limited. The overarching goal of this review is to investigate how adiponectin signaling may ameliorate pathology associated with dystrophin deficiency through inflammatory-dependent and -independent mechanisms, and to determine if current data supports their future progression to clinical trials.

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Section: Discussionsupporting

confidence: 85%

Recent Advances in Pre-clinical Development of Adiponectin Receptor Agonist Therapies for Duchenne Muscular Dystrophy

Gandhi,

Sweeney,

Perry

2024

Preprint

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“…Cytokines are proteins of molecular weight between 15 and 20 kDa that interplay with the development and activity of the immune system, such as interleukins (ILs), tumor necrosis factor alpha (TNF-α), interferon (IFN-γ), and transforming growth factor-beta 1 (TGF-β1). They play an essential role in paracrine, autocrine, and endocrine signaling [ 36 ]. Interleukin 6 (IL-6) is one of the interleukins secreted by leukocytes and the most studied in kidney disease due to its pro-inflammatory effects.…”

Section: Primary Pathogenic Mechanisms Of Ckdmentioning

confidence: 99%

Therapeutic Potential of Photobiomodulation for Chronic Kidney Disease

Bean

Liebert

Bicknell

et al. 2022

IJMS

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Chronic kidney disease (CKD) is a growing global public health problem. The implementation of evidence-based clinical practices only defers the development of kidney failure. Death, transplantation, or dialysis are the consequences of kidney failure, resulting in a significant burden on the health system. Hence, innovative therapeutic strategies are urgently needed due to the limitations of current interventions. Photobiomodulation (PBM), a form of non-thermal light therapy, effectively mitigates mitochondrial dysfunction, reactive oxidative stress, inflammation, and gut microbiota dysbiosis, all of which are inherent in CKD. Preliminary studies suggest the benefits of PBM in multiple diseases, including CKD. Hence, this review will provide a concise summary of the underlying action mechanisms of PBM and its potential therapeutic effects on CKD. Based on the findings, PBM may represent a novel, non-invasive and non-pharmacological therapy for CKD, although more studies are necessary before PBM can be widely recommended.

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“…10 There is evidence for an important role of IL-6 in lipid cardiac metabolism. 11,12 Physiologically, most (even 95%) of energy in cardiomyocytes is derived from phosphorylation processes occurring in mitochondria (predominantly from fatty acids and, to a lesser extent, carbohydrate metabolism), with the remainder coming from process of glycolysis. [13][14][15] Interleukin 6 is involved in maintaining the balance between fatty acid oxidation and cardiac lipotoxicity, where its deficiency results in intracellular toxic lipid accumulation, thereby precipitating mitochondrial oxidative phosphorylation and thus overall cardiac dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Platelet sTWEAK and plasma IL-6 are associated with 18F-fluorodeoxyglucose uptake in right ventricles of patients with pulmonary arterial hypertension: A pilot study

Kazimierczyk¹,

Szumowski²,

Nekolla³

et al. 2022

Adv Clin Exp Med

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Background. Cytokines soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and interleukin 6 (IL-6) are involved in immune response, proliferation, apoptosis, and cardiovascular pathologies. We have previously confirmed that changes of their platelet or plasma contents are associated with pulmonary arterial hypertension (PAH). The positron emission tomography/magnetic resonance imaging (PET/MRI) hybrid imaging provides detailed insight into right ventricle (RV) hemodynamic and metabolic function.Objectives. To evaluate the relationship between RV parameters obtained using PET/MRI and concentrations of plasma and platelet sTWEAK and IL-6 in stable PAH patients. Materials and methods.Eighteen stable PAH patients (48.44 ±16.7 years) had simultaneous PET/MRI scans with 18F-fluorodeoxyglucose ( 18 F-FDG) performed. Its uptake was presented as a standardized uptake value (SUV) for RV and left ventricle (LV). Cytokines concentrations were measured in platelet-poor plasma and platelet lysate. Follow-up time of this study was 58 months; the combined endpoint (CEP) was defined as death or clinical deterioration. Results.We observed significant correlations between platelet sTWEAK levels, plasma IL-6 and PET parameter SUV RV/LV (r = −0.57, p = 0.011; r = 0.50, p = 0.032, respectively). In logistic regression, platelet sTWEAK and IL-6 were both prognostic factors for unfavorable ratio of SUV RV/LV higher than 1 (hazard ratio (HR) = 0.44, 95% confidence interval (95% CI): [0.23; 0.84], p = 0.017; and HR = 3.62, 95% CI: [1.21; 10. 17], p = 0.011, respectively). Furthermore, their concentrations were related with prognostically important higher late gadolinium enhancement mass index (LGEMI) and RV global longitudinal strain/systolic pulmonary artery pressure (RV GLS/sPAP) values. Patients who had CEP in follow-up (n = 13) had significantly lower platelet sTWEAK content and higher plasma IL-6 at baseline than stable patients. Lower platelet sTWEAK was related to a worse prognosis in log-rank test (p = 0.006). Platelet sTWEAK and plasma IL-6 together with RV GLS/sPAP, RV ejection fraction (RVEF), mean pulmonary arterial pressure (mPAP), and SUV RV/LV were significantly associated with time to CEP in univariate Cox analysis.Conclusions. The sTWEAK and IL-6 concentrations in PAH patients are linked with metabolic and functional changes of RV visualized in PET/MRI, and both sTWEAK and IL-6 predict clinical deterioration.

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IL-6 family cytokines as potential therapeutic strategies to treat metabolic diseases

Cited by 9 publications

References 102 publications

Recent Advances in Pre-clinical Development of Adiponectin Receptor Agonist Therapies for Duchenne Muscular Dystrophy

Recent Advances in Pre-clinical Development of Adiponectin Receptor Agonist Therapies for Duchenne Muscular Dystrophy

Therapeutic Potential of Photobiomodulation for Chronic Kidney Disease

Platelet sTWEAK and plasma IL-6 are associated with 18F-fluorodeoxyglucose uptake in right ventricles of patients with pulmonary arterial hypertension: A pilot study

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