Table 1.

Sequelae of chronic inflammatory diseases in the light of altered energy regulation. References that demonstrate the respective disease sequelae and the pathophysiological explanation can be found in detail in reference (1).

Disease sequelae	Pathophysiological elements in chronic inflammation leading to energy allocation to an activated immune system
Depressive symptoms / fatigue	Cytokine (e.g. IL–1β) – driven sickness behavior and fatigue which increase time at rest (muscles and brain in an inactive state).
Anorexia	Consequence of sickness–behavior
Malnutrition	Consequence of anorexia and sickness behavior
Muscle wasting – cachexia	Protein breakdown in muscles as a consequence of anorexia, sickness behavior and androgen deficit
Cachectic obesity	Protein breakdown in muscles as a consequence of anorexia and sickness behavior (protein breakdown > fat breakdown)
Insulin (IGF–1) resistance (with hyperinsulinemia)	Cytokine (e.g. TNF) – induced insulin signaling defects in liver, muscle, and fat tissue but not in immune cells. Immune cells need insulin so that high insulin levels support the activity of the immune system (similar for IGF–1).
Dyslipidemia*	Cytokine – driven acute phase reaction of lipid metabolism leading to higher delivery of cholesterol and other lipids to macrophages
Increase of adipose tissue in the proximity of inflammatorylesions	Presence of adipose tissue surrounding lymph nodes and in the proximity of inflammatory lesions reflects a local store of energy– rich fuels (increased local estrogens might be important to drive local accumulation of adipose tissue). Adipokines play a proinflammatory role.
Alterations of steroid hormone axes	Cytokine / leptin –driven hypoandrogenemia supports muscle breakdown and protein delivery for gluconeogenesis and support of an activated immune system (alanine, glutamine). Cortisol–to–androgen preponderance in chronic inflammation is catabolic.
Elevated sympathetic tone and local sympathetic nerve fiber loss	Cytokine – driven increase of SNS activity increases gluconeogenesis and lipolysis. The parallel loss of sympathetic nerve fibers in inflamed tissue supports local inflammation. It also stimulates lipolysis in the surrounding adipose tissue because sympathetic nerve fibers are increased there.
Hypertension	Cytokine – driven activation of the water retention system due to systemic water loss during inflammation
Decreased parasympathetic tone	Cytokine–driven decrease of the PSNS activity supports allocation of energy–rich fuels to an activated immune system.

^*Dyslipidemia in chronic inflammation reflects low levels of HDL cholesterol and/or apolipoprotein A–I and appearance of an “inflammatory HDL subfraction” with increased serum amyloid A and ceruloplasmin.

Abbreviations: HPA axis, hypothalamic–pituitary adrenal axis; IGF, insulin–like growth factor; IL, interleukin; PSNS, parasympathetic nervous system; SNS, sympathetic nervous system; TNF, tumor necrosis factor.