Concepts of evolutionary medicine and energy regulation contribute to the etiology of systemic chronic inflammatory diseases.

The etiology of chronic inflammatory diseases (CIDs) is usually based on four criteria: (1) genetic susceptibility, (2) complex environmental priming, (3) exaggerated and continuous immune response against harmless self or foreign antigen, and (4) tissue destruction with a continuous wound response without proper healing but with a fibrotic scarring response. These elements do not include the systemic components of CIDs. Due to improved health care with excellent therapies in CIDs, it becomes more and more clear that many systemic responses need to be future targets of therapies. It is suggested that "the systemic response" should be added to the four etiologic criteria that constitute the full picture of CIDs. As shown in the present review, the systemic response becomes comprehensible in the context of evolutionary medicine and energy regulation. Next to the brain and muscles, the immune system is the third major energy consumer in the body. In the context of long-term activation of the immune system during CIDs, the subsequent stimulation of systemic neuroendocrine pathways is necessary to re-allocate energy-rich fuels to the activated immune system. However, re-allocation of energy-rich fuels is the basis of systemic disease sequelae of CIDs, one of which is the metabolic syndrome. It is suggested that Selye's alarm reaction of the 1930s, which is necessary to re-allocate energy-rich fuels to the body, should be called "energy appeal reaction". In CIDs, a continuous energy appeal reaction triggers systemic detrimental consequences for the rest of the body.