Chronic inflammatory systemic diseases – an evolutionary trade-off between acutely beneficial but chronically harmful programs
Résumé
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 nonspecificity
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 energydemanding
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.