Psychoemotional disorders such as depression and anxiety are associated with adverse life experiences, but the precise mechanisms underlying the induction of psychopathologies, particularly anxiety, remain unclear. Among the wide range of biological alterations triggered by stressors, two systems – the hypothalamic–pituitary–adrenocortical (HPA) axis and the immune system – have been most extensively studied. Activation of the HPA axis leads to a rapid increase in glucocorticoids (cortisol in humans and corticosterone in rodents), which play a central role in coordinating adaptive stress responses. However, this increase can also lead to the development of psychopathologies. Elevated levels of peripheral and central proinflammatory cytokines have been reported in both patients with anxiety symptoms and laboratory animals. Elucidating the contribution of immune and glucocorticoid responses to stress-related behavioral outcomes is complicated by complex and bidirectional interactions between these systems. While corticosterone, consistent with the well-established immunosuppressive activity of glucocorticoids, can exert anti-inflammatory effects, elevated levels of this hormone may also promote systemic inflammation by enhancing the production of proinflammatory cytokines. Conversely, cytokines can modulate HPA axis activity, further influencing stress responses. The review summarizes experimental evidence on the roles of glucocorticoid hormones and the key proinflammatory cytokine interleukin-1β (IL-1β), as well as their interactions, in the development of stress-induced anxiety. A better understanding of these mechanisms may help clarify the pathophysiology of anxiety disorders.
Vysotskaya et al. (Fri,) studied this question.