Old Friends, immunoregulation, and stress resilience

Abstract

There is a considerable body of evidence indicating that chronic adverse experience, especially chronic psychosocial stress/trauma, represents a major risk factor for the development of many somatic and affective disorders, including inflammatory bowel disease (IBD) and posttraumatic stress disorder (PTSD). However, the mechanisms underlying the development of chronic stress-associated disorders are still in large part unknown, and current treatment and prevention strategies lack efficacy and reliability. A greater understanding of mechanisms involved in the development and persistence of chronic stress-induced disorders may lead to novel approaches to prevention and treatment of these disorders. In this review, we provide evidence indicating that increases in immune (re-)activity and inflammation, potentially promoted by a reduced exposure to immunoregulatory microorganisms ("Old Friends") in today's modern society, may be causal factors in mediating the vulnerability to development and persistence of stress-related pathologies. Moreover, we discuss strategies to increase immunoregulatory processes and attenuate inflammation, as for instance contact with immunoregulatory Old Friends, which appears to be a promising strategy to promote stress resilience and to prevent/treat chronic stress-related disorders.

Keywords: Cortisol; Inflammation; Interleukin (IL)-6; Old Friends; Trier Social Stress Test (TSST); Urban versus rural.

Fig. 1

Hypothetical model illustrating how areas offering a narrow (right panel) relative to a wide (left panel) range of microbial exposures promote stress vulnerability and compromise stress resilience. Reduced exposure to immunoregulatory Old Friends, especially during early life, result in an exaggerated and long-lasting immune response towards any acute psychosocial stressor (indicated by the flash symbol in the gray arrow) faced during adulthood, over time resulting in constant immune activation and chronic low-grade inflammation and, consequently, in the development of a variety of stress-associated somatic and psychiatric disorders in which chronic, low-level inflammation is a risk factor. (Photograph on left side © Xaver Linder)