The DOI matches its Crossref record; 162 of the 165 references it cites were found in a registry or an index.
The central role of hypothalamic inflammation in the acute illness response and cachexia
Open accessAbstract
When challenged with a variety of inflammatory threats, multiple systems across the body undergo physiological responses to promote defense and survival. The constellation of fever, anorexia, and fatigue is known as the acute illness response, and represents an adaptive behavioral and physiological reaction to stimuli such as infection. On the other end of the spectrum, cachexia is a deadly and clinically challenging syndrome involving anorexia, fatigue, and muscle wasting. Both of these processes are governed by inflammatory mediators including cytokines, chemokines, and immune cells. Though the effects of cachexia can be partially explained by direct effects of disease processes on wasting tissues, a growing body of evidence shows the central nervous system (CNS) also plays an essential mechanistic role in cachexia. In the context of inflammatory stress, the hypothalamus integrates signals from peripheral systems, which it translates into neuroendocrine perturbations, altered neuronal signaling, and global metabolic derangements. Therefore, we will discuss how hypothalamic inflammation is an essential driver of both the acute illness response and cachexia, and why this organ is uniquely equipped to generate and maintain chronic inflammation. First, we will focus on the role of the hypothalamus in acute responses to dietary and infectious stimuli. Next, we will discuss the role of cytokines in driving homeostatic disequilibrium, resulting in muscle wasting, anorexia, and weight loss. Finally, we will address mechanisms and mediators of chronic hypothalamic inflammation, including endothelial cells, chemokines, and peripheral leukocytes.
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“The primary stress response axis, the hypothalamic-pituitary-adrenal (HPA) axis, can be stimulated by peripheral inflammatory responses to infection or trauma resulting in the sympathetic activation of a positive feedback loop whereby hypothalamic inflammatory signaling drives and is sustained by local production of IL-1β, IL-6, and TNFα10.”
From Leveraging Prior Knowledge of Endocrine Immune Regulation in the Therapeutically-relevant Phenotyping of Women with Chronic Fatigue Syndrome (2019) · cites this paper as [10]
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Cites
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,526
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
Identification of ubiquitin ligases required for skeletal muscle atrophy.
Bodine, S. C., Latres, E., Baumhueter, S., Lai, V. K.-M., Nunez, L., Clarke, B. A., Poueymirou, W. T., Panaro, F. J., Na, E., Dharmarajan, K., et al. (2001) · Science · doi:10.1126/science.1065874 · Cited by 3,521
The complexity of NF-κB signaling in inflammation and cancer
Hoesel, B., & Schmid, J. A. (2013) · Molecular Cancer · doi:10.1186/1476-4598-12-86 · Cited by 3,277
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Yona, S., Kim, K.-W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.12.001 · Cited by 3,245
Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress
Tsigos, C., & Chrousos, G. P. (2002) · Journal of Psychosomatic Research · doi:10.1016/s0022-3999(02)00429-4 · Cited by 2,822 · cited 1×
“Direct stimulation by ACTH causes production and release of cortisol from the zona fasiculata of the adrenal cortex [36].”
BackgroundElevated Circulating Levels of Tumor Necrosis Factor in Severe Chronic Heart Failure
Levine, B., Kalman, J., Mayer, L., Fillit, H. M., & Packer, M. (1990) · New England Journal of Medicine · doi:10.1056/nejm199007263230405 · Cited by 2,582 · cited 1×
“Furthermore, elevated circulating levels of TNFα and IL-6 in cardiac cachexia are the strongest predictor for pathological weight loss [75,76].”
BackgroundCentral nervous system control of food intake and body weight
Morton, G. J., Cummings, D. E., Baskin, D. G., Barsh, G. S., & Schwartz, M. W. (2006) · Nature · doi:10.1038/nature05026 · Cited by 2,503
Tatemoto, K., Carlquist, M., & Mutt, V. (1982) · Nature · doi:10.1038/296659a0 · Cited by 2,254
Obesity is associated with hypothalamic injury in rodents and humans.
Thaler, J. P., Yi, C.-X., Schur, E. A., Guyenet, S. J., Hwang, B. H., Dietrich, M. O., Zhao, X., Sarruf, D. A., Izgur, V., Maravilla, K. R., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59660 · Cited by 1,857
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Baracos, V. E., Martin, L., Korc, M., Guttridge, D. C., & Fearon, K. C. H. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.105 · Cited by 1,738
Cancer cachexia and its pathophysiology: links with sarcopenia, anorexia and asthenia
da Silva, S. P., Santos, J., Silva, M. P. C. E., da Costa, R. M. G., & Medeiros, R. (2020) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12528 · Cited by 392
Potential of plant polyphenols to combat oxidative stress and inflammatory processes in farm animals
Geßner, D. K., Ringseis, R., & Eder, K. (2016) · Journal of Animal Physiology and Animal Nutrition · doi:10.1111/jpn.12579 · Cited by 370
Inter-tissue communication in cancer cachexia
Argilés, J. M. A., Stemmler, B., López-Soriano, F. J., & Busquets, S. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0123-0 · Cited by 317
Antibody-mediated inhibition of GDF15–GFRAL activity reverses cancer cachexia in mice
Suriben, R., Chen, M. J., Higbee, J., Oeffinger, J., Ventura, R., Li, B., Mondal, K., Gao, Z., Ayupova, D. A., Taskar, P., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0945-x · Cited by 311
Metadata
- Authors
- Burfeind, K. G., Michaelis, K. A., & Marks, D. L.
- Affiliations
- Oregon Health & Science University (US)
- Corresponding author
- Marks, Daniel L.
- Venue
- Seminars in Cell & Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 54
- Pages
- 42-52
- ISSN
- 1084-9521 (ISSN-L)
- PMC
- PMC4872506
- OpenAlex
- W2189988755
- Cited by
- 156
- References
- 165
- Citations by year
- 2026: 7 · 2025: 20 · 2024: 13 · 2023: 15 · 2022: 18 · 2021: 24 · 2020: 17 · 2019: 15 · 2018: 11 · 2017: 10 · 2016: 6
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Seminars in Cell and Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA184324)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- hypothalamic inflammation, cachexia, fever, anorexia, fatigue, cytokines, chemokines, muscle atrophy, weight loss, chronic inflammation, neuroendocrine regulation, endothelial cells, peripheral blood leukocytes, infection, nutritional stress
- MeSH terms
- Animals, Cachexia, Humans, Hypothalamus, Inflammation, Models, Biological, Obesity, Muscle, Skeletal
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