Homeostasis, Inflammation, and Disease Susceptibility

By M. Kotas, R. Medzhitov. Cell, 2015

1,071 citations recorded by the source corpus.

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.

Subfields: Endocrine and Autonomic Systems, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/d6a09754f32ed1df4c1d4e58fc4ae12c8be91c73

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrine and Autonomic Systems

1. T. Pradeu

In Epidemiology

1. Luciana Besedovsky
2. T. Lange
3. M. Haack
4. T. Pradeu

In Physiology

1. Luciana Besedovsky
2. T. Lange
3. T. Pradeu

Citations in the corpus

• Inflammation and aging: signaling pathways and intervention therapies (2023, background): “This inflammation hampers intrinsic cellular repair mechanisms following injury and promotes immunosenescence and organ damage.(151,152) Elderly individuals exhibit immunological phenotypes characterized by reduced numbers of naive lymphocytes, increased proinflammatory T cells, and diminished phago”
• Organisms or biological individuals? Combining physiological and evolutionary individuality (2016, background): “Recent views extend these physiological approaches to individuality via different conceptual and theoretical tools, from systems biology in cardiology (Noble 2006; Noble 2008) to control theory and systems dynamics theory in the study of inflammation (Kotas and Medzhitov 2015).”
• DUSP11-mediated control of 5′-triphosphate RNA regulates RIG-I sensitivity (2020, background): “Life is a great balancing act with overlapping and unique molecular controls required to maintain homeostasis (Kotas and Medzhitov 2015; tenOever 2016).”
• The Multifaceted Role of Annexin A1 in Viral Infections (2023, background): “The recruitment of leukocytes to the affected tissue site and the production of specific mediators are common features of the inflammatory process, which may or may not result in the impairment of the primary functions of the affected organ [29,30].”
• The Sleep-Immune Crosstalk in Health and Disease (2019, background): “The typical inflammatory response is triggered by a local infection or tissue injury, involving PAMPs and DAMPs, and is traditionally thought of as a protective reaction that defends and restores physiological functions (111, 296).”