Figure 2.

There is a critical difference between typical inflammation and chronic inflammatory systemic diseases, which separates the asymptomatic phase from the symptomatic phase of a chronic inflammatory systemic disease, the asymptomatic-symptomatic-threshold (a-s-threshold). Importantly from an evolutionary point of view, reproduction is only impeded during the symptomatic, but not during the asymptomatic phase. Genes enabling an adaptive inflammatory response, allowing the organism to overcome an infection, will thus increase survival probability and the potential for future reproduction and as such evolutionary fitness in young age. After initiation of chronic systemic inflammation, however, reproduction is inhibited, and this for prolonged periods, often for years and until death, causing fitness costs. However, as these costs typically occur only at the end of the reproductive life-history stage or in post-reproductive age, these fitness costs are lower than the fitness benefits in early life leading to an overall increase in Darwinian fitness