The immune system, which evolved as a protective system, can paradoxically mediate lethal effects when it is over-activated. These effects can be traced back to infected insects and are mainly mediated by phylogenetically old cytokines that have been found already in starfishes and sponges. We hypothesize that these anti-homeostatic effects are important for restricting the cumulative risk of transmission of highly mutating environmental pathogens that may endanger species, particularly when they start to originate and expand. Considering the Darwinian view that evolution is a permanent process, this anti-homeostatic program is preserved and expressed even when there is no risk for the species. Here, we review these aspects and discuss how evolutionary-imposed anti-homeostatic immune programs are expressed during acute and chronic human diseases, which can be further aggravated in the absence of medical interventions. The relevance of early identification of ancestral biomarkers that predict a shift from protective to deleterious immune outcomes is emphasized.

免疫系统是作为保护系统进化而来的，但当它过度激活时，却可以自相矛盾地介导致死作用。这些影响可以追溯到受感染的昆虫，并且主要由已经在海星和海绵中发现的系统发育古老的细胞因子介导。我们假设这些抗稳态效应对于限制可能危及物种的高度变异环境病原体传播的累积风险很重要，特别是当它们开始起源和扩展时。考虑到进化是一个永久过程的达尔文主义观点，即使物种没有风险，这种反稳态程序也会被保留和表达。在这里，我们回顾了这些方面并讨论了进化强加的抗稳态免疫程序如何在急性和慢性人类疾病中表达，如果没有医疗干预，情况可能会进一步恶化。强调了早期识别预测从保护性免疫结果转变为有害免疫结果的祖先生物标志物的相关性。