ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2016
Combined Metabolomics and Transcriptomics Approaches to Assess the IL-6 Blockade as a Therapeutic of ALS: Deleterious Alteration of Lipid Metabolism.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Inflammatory checkpoints in amyotrophic lateral sclerosis: From biomarkers to therapeutic targets.Frontiers in immunology · 2022Pooled it
- Mitochondria: A Promising Convergent Target for the Treatment of Amyotrophic Lateral Sclerosis.Cells · 2024Review
- Metabolic Profile and Pathological Alterations in the Muscle of Patients with Early-Stage Amyotrophic Lateral Sclerosis.Biomedicines · 2022Article
- BMP/TGF-β signaling as a modulator of neurodegeneration in ALS.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- New insight into neurological degeneration: Inflammatory cytokines and blood-brain barrier.Frontiers in molecular neuroscience · 2022Review
- Fibrinogen-Like Protein 1 as a Novel Biomarker of Psoriasis Severity.Journal of inflammation research · 2022Article
- Elevation of Serum Cytokine Profiles and Liver Metabolomic Normalization in Early Convalescence of COVID-19 Patients.Frontiers in medicine · 2021Article
- Conditioned Medium from Cells Overexpressing TDP-43 Alters the Metabolome of Recipient Cells.Cells · 2020Article
- Metabolomics: A Tool to Understand the Impact of Genetic Mutations in Amyotrophic Lateral Sclerosis.Genes · 2020Review
- Transcriptomics and Metabolomics in Amyotrophic Lateral Sclerosis.Advances in experimental medicine and biology · 2020Review
- Article
- Hochu-Ekki-To Improves Motor Function in an Amyotrophic Lateral Sclerosis Animal Model.Nutrients · 2019Article
- Metabolomics Coupled with Transcriptomics Approach Deciphering Age Relevance in Sepsis.Aging and disease · 2019Article
- Astrocyte alterations in neurodegenerative pathologies and their modeling in human induced pluripotent stem cell platforms.Cellular and molecular life sciences : CMLS · 2019Review
- Are Circulating Cytokines Reliable Biomarkers for Amyotrophic Lateral Sclerosis?International journal of molecular sciences · 2019Review
- Metabolic and Stress Response Changes Precede Disease Onset in the Spinal Cord of Mutant SOD1 ALS Mice.Frontiers in neuroscience · 2019Article
- Therapeutic Strategies Under Development Targeting Inflammatory Mechanisms in Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2018Review
- Potential Role of Humoral IL-6 Cytokine in Mediating Pro-Inflammatory Endothelial Cell Response in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2018Review
- Sphingolipid Metabolism Is Dysregulated at Transcriptomic and Metabolic Levels in the Spinal Cord of an Animal Model of Amyotrophic Lateral Sclerosis.Frontiers in molecular neuroscience · 2017Article
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Authors and funding
17 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In amyotrophic lateral sclerosis (ALS), motor neuron degeneration occurs simultaneously with systemic metabolic impairment and neuroinflammation. Playing an important role in the regulation of both phenomena, interleukin (IL)-6, a major cytokine of the inflammatory response has been proposed as a target for management of ALS. Although a pilot clinical trial provided promising results in humans, another recent preclinical study showed that knocking out the IL-6 gene in mice carrying ALS did not improve clinical outcome. In this study, we aimed to determine the relevance of the IL-6 pathway blockade in a mouse model of ALS by using a pharmacological antagonist of IL-6, a murine surrogate of tocilizumab, namely MR16-1. We analyzed the immunological and metabolic effects of IL-6 blockade by cytokine measurement, blood cell immunophenotyping, targeted metabolomics, and transcriptomics. A deleterious clinical effect of MR16-1 was revealed, with a speeding up of weight loss (p = 0.0041) and decreasing body weight (p < 0.05). A significant increase in regulatory T-cell count (p = 0.0268) and a decrease in C-X-C ligand-1 concentrations in plasma (p = 0.0479) were observed. Metabolomic and transcriptomic analyses revealed that MR16-1 mainly affected branched-chain amino acid, lipid, arginine, and proline metabolism. IL-6 blockade negatively affected body weight, despite a moderated anti-inflammatory effect. Metabolic effects of IL-6 were mild compared with metabolic disturbances observed in ALS, but a modification of lipid metabolism by therapy was identified. These results indicate that IL-6 blockade did not improve clinical outcome of a mutant superoxide dismutase 1 mouse model of ALS.
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