GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance
Open accessAbstract
Growth and differentiation factor 15 (GDF15) is an inflammation-associated hormone with poorly defined biology. Here, we investigated the role of GDF15 in bacterial and viral infections. We found that inflammation induced GDF15, and that GDF15 was necessary for surviving both bacterial and viral infections, as well as sepsis. The protective effects of GDF15 were largely independent of pathogen control or the magnitude of inflammatory response, suggesting a role in disease tolerance. Indeed, we found that GDF15 was required for hepatic sympathetic outflow and triglyceride metabolism. Failure to defend the lower limit of plasma triglyceride levels was associated with impaired cardiac function and maintenance of body temperature, effects that could be rescued by exogenous administration of lipids. Together, we show that GDF15 coordinates tolerance to inflammatory damage through regulation of triglyceride metabolism.
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The mechanism underlying stress-induced worsening of end-organ function and death is likely a result of stress-induced IL6-dependent metabolic re-programming.
“The mechanism underlying this phenomenon is unclear, but likely is a result of stress-induced IL6-dependent metabolic re-programming similar to that which has been previously published by our group and others (Ganeshan et al., 2019; Luan et al., 2019; Wang et al., 2016; Wang A, 2019; Weis et al., 2017).”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Luan et al., 2019
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- Authors
- Luan, H. H., Wang, A., Hilliard, B. K., Carvalho, F., Rosen, C. E., Ahasic, A. M., Herzog, E. L., Kang, I., Pisani, M. A., Yu, S., Zhang, C., Ring, A. M., Young, L. H., & Medzhitov, R.
- Affiliations
- Yale University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Wang, Andrew
- Medzhitov, Ruslan
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 178
- Issue
- 5
- Pages
- 1231-1244.e11
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6863354
- OpenAlex
- W2967524380
- Cited by
- 527
- References
- 68
- Citations by year
- 2026: 77 · 2025: 80 · 2024: 69 · 2023: 72 · 2022: 81 · 2021: 59 · 2020: 75 · 2019: 12
- FWCI
- 43.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Foundation for the National Institutes of Health
- Topics
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- GDF15, growth and differentiation factor 15, disease tolerance, inflammation, bacterial infection, viral infection, sepsis, triglyceride metabolism, cardiac function, body temperature, lipid supplementation
- MeSH terms
- Animals, Antibodies, Disease Models, Animal, Heart, Humans, Lipopolysaccharides, Liver, Mice, Inbred C57BL, Norepinephrine, Orthomyxoviridae, Poly I-C, Recombinant Proteins, Triglycerides, Tumor Necrosis Factor-alpha, Survival Rate, Sepsis, Troponin I, Lipid Metabolism, Mice, Growth Differentiation Factor 15
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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