Energy Balance and Neuroendocrine-Immune Regulation in Chronic Inflammatory and Neoplastic Diseases: An Evolutionary Perspective

Abstract

The central nervous and immune systems are often in competition for energy substrates. After infection or injury, energy expenditure typically increases while exploratory behavior and food intake decrease (sickness behavior). However, in the absence of food intake, animal bodies can only sustain increased expenditure for 3–7 weeks before energy substrates run out. Nevertheless, symptoms reminiscent of wasting and sickness behavior can be observed in autoimmunity, and in chronic inflammatory or brain-related disorders. The hypothesis defended here is that chronic diseases can exist because they mostly occur after reproductive age and involve responses that were selected during evolution in response to acute infection and injury. Indeed, fever and reduced food intake can increase survival in response to acute bacterial infection and are brought about by actions of pro-inflammatory cytokines on the brain, resulting in autonomic, behavioral, and neuroendocrine responses in a context of energy trade-offs. While these responses may be adaptive and actively brought about when an organism responds to acute infection, they seem maladaptive when lasting too long, such as in chronic diseases, as they contribute to a negative energy balance.