Title:Immunomodulation Mechanism of Antidepressants: Interactions between Serotonin/Norepinephrine Balance and Th1/Th2 Balance
Volume: 10
Issue: 2
Author(s): Matteo Martino, Giulio Rocchi, Andrea Escelsior and Michele Fornaro
Affiliation:
Keywords:
Antidepressants, cytokines, neurotransmitters, receptors, Th1, Th2
Abstract: Neurotransmitters and hormones regulate major immune functions, including the selection of T helper (Th)1 or
Th2 cytokine responses, related to cell-mediated and humoral immunity, respectively. A role of imbalance and dynamic
switching of Th1/Th2 system has been proposed, with relative displacement of the immune reserve in relation to complex
interaction between Th1/Th2 and neuro-hormonal balance fluctuations, in the pathogenesis of various chronic human
diseases, probably also including psychiatric disorders. Components of the stress system such as norepinephrine (NE) and
glucocorticoids appear to mediate a Th2 shift, while serotonin (5-HT) and melatonin might mediate a Th1 shift. Some
antidepressants would occur affecting these systems, acting on neurotransmitter balance (especially the 5-HT/NE balance)
and expression levels of receptor subtypes, which in turn affect cytokine production and relative Th1/Th2 balance. It
could be therefore hypothesized that the antidepressant-related increase in NE tone enhances the Th2 response, while the
decrease in NE tone or the increase in 5-HT tone enhances the Th1 response. However, the neurotransmitter and Th1/Th2
balance modulation could be relative, aiming to restore physiological levels a previous imbalance in receptor sensitivity
and cytokine production. The considerations on neuro-immunomodulation could represent an additional aid in the study
of pathophysiology of psychiatric disorders and in the choice of specific antidepressants in specific clusters of symptoms,
especially in comorbidity with internal pathologies. Furthermore limited data, reviewed here, have shown the
effectiveness of some antidepressants as pure immunomodulators. However, these considerations are tentative and require
experimental confirmation or refutation by future studies.
