title: Chronic inflammatory systemic diseases: An evolutionary trade-off between acutely beneficial but chronically harmful programs.
abstract: It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3-8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting-cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs.
authors.affiliation: Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Division of Rheumatology, Department of Internal Medicine, University Hospital Regensburg, Regensburg, Germany; rainer.straub@ukr.de.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
authors.affiliation: Université De Strasbourg, IPHC-DEPE, 23 Rue Becquerel, Strasbourg 67087, France; CNRS (Centre National De La Recherche Scientifique), UMR7178, Strasbourg 67087, France; School of Animal, Plant and Environmental Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schradin
keywords: disease sequelae; energy regulation; inflammatory systemic disease; neuroendocrine immunology
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