Evolution, Energy and Chronic Inflammatory Disease

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

By Straub RH.  Laboratory of Experimental Rheumatology and Neuroendocrino-Immunology, Division of Rheumatology, Department of Internal Medicine I, University Hospital Regensburg, Germany.

Brain Behav Immun. 2010 Aug 9. [Epub ahead of print] (not open access)
Abstract
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.

Also see open access content at  Journal of Internal Medicine Volume 267,  Issue 6, pages 543–560, June 2010 Energy regulation and neuroendocrine–immune control in chronic inflammatory diseases R. H. Straub¹,  M. Cutolo²,  F. Buttgereit³,  G. Pongratz¹ Article first published online: 28 JAN 2010 DOI: 10.1111/j.1365-2796.2010.02218.x

Abstract:

Energy regulation (EnR) is most important for homoeostatic regulation of physiological processes. Neuroendocrine pathways are involved in EnR. We can separate factors that provide energy-rich fuels to stores [parasympathetic nervous system (PSNS), insulin, insulin-like growth factor-1, oestrogens, androgens and osteocalcin] and those that provide energy-rich substrates to consumers [sympathetic nervous system (SNS), hypothalamic–pituitary–adrenal axis, thyroid hormones, glucagon and growth hormone]. In chronic inflammatory diseases (CIDs), balanced energy-rich fuel allocation to stores and consumers, normally aligned with circadian rhythms, is largely disturbed due to the vast fuel consumption of an activated immune system (up to 2000 kJ day⁻¹). Proinflammatory cytokines such as tumour necrosis factor or interleukins 1β and 6, circulating activated immune cells and sensory nerve fibres signal immune activation to the rest of the body. This signal is an appeal for energy-rich fuels as regulators are switched on to supply energy-rich fuels (‘energy appeal reaction’). During evolution, adequate EnR evolved to cope with nonlife-threatening diseases, not with CIDs (huge negative selection pressure and reduced reproduction). Thus, EnR is inadequate in CIDs leading to many abnormalities, including sickness behaviour, anorexia, hypovitaminosis D, cachexia, cachectic obesity, insulin resistance, hyperinsulinaemia, dyslipidaemia, fat deposits near inflamed tissue, hypoandrogenaemia, mild hypercortisolaemia, activation of the SNS (hypertension), CID-related anaemia and osteopenia. Many of these conditions can contribute to the metabolic syndrome. These signs and symptoms become comprehensible in the context of an exaggerated call for energy-rich fuels by the immune system. We propose that the presented pathophysiological framework may lead to new therapeutical approaches and to a better understanding of CID sequence.