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The brain and immune system prompt energy shortage in chronic inflammation and ageing


Sequelae frequently seen in patients with chronic inflammatory diseases, such as fatigue, depressed mood, sleep alterations, loss of appetite, muscle wasting, cachectic obesity, bone loss and hypertension, can be the result of energy shortages caused by an overactive immune system. These sequelae can also be found in patients with chronic inflammatory diseases that are in remission and in ageing individuals, despite the immune system being less active in these situations. This Perspectives article proposes a new way of understanding situations of chronic inflammation (such as rheumatic diseases) and ageing based on the principles of evolutionary medicine, energy regulation and neuroendocrine–immune crosstalk. A conceptual framework is provided to enable physicians and scientists to better understand the signs and symptoms of chronic inflammatory diseases and long-term disease consequences resulting from physical and mental inactivity.

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Figure 1: Regulation of energy storage and energy release.
Figure 2: Average total energy expenditure for adults under various conditions.
Figure 3: The adaptive and maladaptive energy matrices.


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R.H.S. would like to thank David Pisetsky of Duke University Medical Center, Durham, North Carolina, USA, who reviewed an early version of the manuscript and provided helpful editorial comments, and the team of Martin Fleck at University Hospital Regensburg, Regensburg, Germany, for discussing the clinical aspects of the present work during a seminar in 2016. The work of R.H.S. is supported financially by the Deutsche Forschungsgemeinschaft (DFG), the German Federal Ministry of Education and Research and the State of Bavaria (through local funding by University Hospital Regensburg).

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Correspondence to Rainer H. Straub.

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Supplementary information

Supplementary information S1 (table)

Adaptive programmes in chronic inflammatory diseases and during ageing that protect against energy shortages (PDF 72 kb)

PowerPoint slides


Context-associated anorexia

Anorexia that is dependent on a particular circumstance, such as sickness behaviour during an infection, mental activation in bipolar disorder or age-related anorexia.

Insulin resistance

A condition of low insulin sensitivity with marked changes to the insulin receptor and to downstream signalling pathways; because insulin is responsible for the storage of glucose and free fatty acids, a lower insulin sensitivity leads to reduced energy storage and increased levels of energy-rich fuels in the circulation.

Pro-inflammatory load

A high level of systemic activity in the immune system, as measured by an increased erythrocyte sedimentation rate, or increased levels of serum C-reactive protein or serum IL-6.

Psychomotor activity

Activity induced by the brain that leads to activation of the skeletal muscles and the heart.


Integrative systems at the top level of homeostatic regulation of the body; examples include the nervous, endocrine and immune systems.

Thermodynamically open system

Systems, such as the human body, that can take up and lose energy, mainly in the form of heat.

State and trait anxiety

State anxiety is how a person is feeling at the time of a perceived threat, whereas trait anxiety is the enduring disposition to feel stress, worry and discomfort.

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Straub, R. The brain and immune system prompt energy shortage in chronic inflammation and ageing. Nat Rev Rheumatol 13, 743–751 (2017).

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