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Cell. 2015 Feb 26;160(5):816-827. doi: 10.1016/j.cell.2015.02.010.

Homeostasis, inflammation, and disease susceptibility.

Author information

1
Department of Immunobiology, Yale University School of Medicine, New Haven, CT USA.
2
Department of Immunobiology, Yale University School of Medicine, New Haven, CT USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT USA. Electronic address: ruslan.medzhitov@yale.edu.

Abstract

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.

PMID:
25723161
PMCID:
PMC4369762
DOI:
10.1016/j.cell.2015.02.010
[Indexed for MEDLINE]
Free PMC Article

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