Molecular links between endocrine, nervous and immune system during chronic stress

Introduction The stress response is different in various individuals, however, the mechanisms that could explain these distinct effects are not well known and the molecular correlates have been considered one at the time. Particular harmful conditions occur if the subject, instead to cope the stressful events, succumb to them, in this case, a cascade reaction happens that through different signaling causes a specific reaction named “sickness behaviour.” The aim of this article is to review the complex relations among important molecules belonging to Central nervous system (CNS), immune system (IS), and endocrine system (ES) during the chronic stress response. Methods After having verified the state of art concerning the function of cortisol, norepinephrine (NE), interleukin (IL)‐1β and melatonin, we describe as they work together. Results We propose a speculative hypothesis concerning the complex interplay of these signaling molecules during chronic stress, highlighting the role of IL‐1β as main biomarker of this effects, indeed, during chronic stress its increment transforms this inflammatory signal into a nervous signal (NE), in turn, this uses the ES (melatonin and cortisol) to counterbalance again IL‐1β. During cortisol resistance, a vicious loop occurs that increments all mediators, unbalancing IS, ES, and CNS networks. This IL‐1β increase would occur above all when the individual succumbs to stressful events, showing the Sickness Behaviour Symptoms. IL‐1β might, through melatonin and vice versa, determine sleep disorders too. Conclusion The molecular links here outlined could explain how stress plays a role in etiopathogenesis of several diseases through this complex interplay. Central nervous system (CNS), immune system (IS), and endocrine system (ES) operate together during the chronic stress response. We propose that this complex molecular network is altered in sickness behaviors.