Table 3

The energy appeal reaction

Known reaction

Physiological meaning in transient inflammatory episodes

Pathophysiological problem in chronic inflammatory diseases


Fatigue

Stop of energy expenditure for brain and muscles, stop of courtship and foraging behavior

Depressive symptoms/longstanding fatigue (sickness behavior)

Anorexia

Stop of energy expenditure for gut function

Reduced or stopped uptake of energy-rich substrates

Malnutrition

Stop of energy expenditure for gut function

Reduced or stopped uptake of vitamins and trace elementsa

Muscle breakdown

Stop of energy expenditure for muscles, and redirection of muscle proteins to gluconeogenesis

Cachexia

Increased muscle relative to fat breakdown

Stop of energy expenditure for muscles, and redirection of muscle proteins to gluconeogenesis

Cachectic obesity

Insulin (insulin-like growth factor-1) resistance in liver, muscle, and fat tissue

Redirection of glucose and free fatty acids to immune cells, which do not become insulin (insulin-like growth factor-1) resistant

Insulin resistance as part of the metabolic syndrome

Appearance of a proinflammatory form of HDL cholesterol

Acute-phase reaction of lipid metabolism leading to higher delivery of cholesterol and other lipids to macrophages

Dyslipidemia as part of the metabolic syndrome

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 and gluconeogenetic

Elevated sympathetic tone and local sympathetic nerve fiber loss, decreased parasympathetic tone

Cytokine-driven increase of sympathetic nervous system activity increases gluconeogenesis and lipolysis. The parallel loss of sympathetic nerve fibers in inflamed tissue supports local inflammation and local lipolysis

Hypertension as part of the metabolic syndrome

Increase of body water

Cytokine-driven activation of the water retention system due to systemic water loss during inflammation

Hypertension as part of the metabolic syndrome

Inflammation-related anemia

Stop of energy expenditure for brain and muscle activity

Anemia

Inflammation-related provision of calcium and phosphorus

High calcium and phosphorus are mandatory for energy-consuming reactions (think of ATP)

Local and general osteopenia


Data taken from [2,90]. HDL, high-density lipoprotein. aHypovitaminosis D and others, deficiency in zinc, iron, copper, magnesium, and similar.

Spies et al. Arthritis Research & Therapy 2012 14:216   doi:10.1186/ar3885