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Kotas, Maya E., & Medzhitov, R. (2015). Homeostasis, Inflammation, and Disease Susceptibility. Cell, 160(5), 816–827. Added by: Dr. Enrique Feoli (16/06/2020, 02:32) Last edited by: Dr. Enrique Feoli (17/02/2026, 20:10) |
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| Resource type: Journal Article DOI: 10.1016/j.cell.2015.02.010 ID no. (ISBN etc.): 928674 BibTeX citation key: Kotas2015 View all bibliographic details  |
Categories: BioAcyl Corp, BioAcyl Corp, Mendeley Subcategories: Bioregulatory systems medicine, Systems Biology, Systems Dynamics Theory Creators: Kotas, Medzhitov Collection: Cell |
Views: 4/528
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| Abstract |
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While modernization has dramatically increased lifespan, it has also witnessed the increasing prevalence of diseases such as obesity, hypertension, and type 2 diabetes. Such chronic, acquired diseases result when normal physiologic control goes awry and may thus be viewed as failures of homeostasis. However, while nearly every process in human physiology relies on homeostatic mechanisms for stability, only some have demonstrated vulnerability to dysregulation. Additionally, chronic inflammation is a common accomplice of the diseases of homeostasis, yet the basis for this connection is not fully understood. Here we review the design of homeostatic systems and discuss universal features of control circuits that operate at the cellular, tissue, and organismal levels. We suggest a framework for classification of homeostatic signals that is based on different classes of homeostatic variables they report on. Finally, we discuss how adaptability of homeostatic systems with adjustable set points creates vulnerability to dysregulation and disease. This framework highlights the fundamental parallels between homeostatic and inflammatory control mechanisms and provides a new perspective on the physiological origin of inflammation.
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| Notes |
(A) Inflammatory signals (IS) act through the same control points (Plants flows and Controller gains) as homeostatic signals (HS). To illustrate the parallels between homeostatic and inflammatory signals, the source of inflammatory signal is referred to as Inflammatory Controller (e.g., macrophage), by analogy to Homeostatic Controller (e.g., endocrine pancreas). (B) Macrophages produce TNF and IL-1 which act on the same flows as insulin, but in opposite direction: TNF and IL-1 induce insulin resistance and suppress lipid storage in adipose tissue by inhibiting lipoprotein lipase. In addition, these cytokines induce gain tuning of the pancreatic β-cells to reduce the amount of insulin produced in response to a given level of blood glucose. This effect is achieved in part by suppressing glucose flow into β-cells.
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Importantly, the inflammatory mediators are both antagonistic to and dominant over homeostatic signals. They are antagonistic because normal homeostasis is often incompatible with the goals of the inflammatory response, and the former has to be temporarily disengaged. Inflammatory signals are dominant because they have higher physiological priority as they orchestrate the protective response to life threatening insults of infection and injury. Thus, homeostatic control of body temperature (thermogenesis or sweating) is normally induced by changes in ambient temperature. However, acute inflammation overrides this control by raising the set point of body temperature, thereby inducing thermogenesis and fever regardless of ambient temperature. Likewise, acute inflammation-induced anorexia suppresses caloric intake regardless of the adiposity, circulating nutrient concentrations, or body weight.
Added by: Dr. Enrique Feoli
(2021-02-11 23:54:26)
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