Serotonin as a Modulator of Immune Function: An Overview

The CNS and immune system interact in a reciprocal manner through a wide variety of common mediators including neurotransmitters and cytokines. Among the former, serotonin (5-Hydroxytryptamine = 5-HT) plays a major role in the control of neuronal activity. It may also control the level of cytokines and lymphocyte proliferation. 5-HT is synthesized and released in the circulation by enterochromaffin cells from gastric and intestinal mucosa. Under inflammatory conditions such as thrombosis and ischemia, the activated platelets release 5-HT at the site of inflammation and lead to an increase in its local concentration. In addition to its possible interaction with blood cells, 5-HT may also interact with the inflamed tissue macrophages through its various receptors. Accordingly, 5-HT transporters and 5-HT receptor subtypes have been characterized in different blood cells. This review provides an overview of reported data on the regulatory role of 5-HT on the activity of peripheral blood cells. Such role includes both immunostimulatory and immunoinhibitory effects based on 5-HT concentration and its cellular target. In the light of recent data, this review also speculates on the intracellular processes (i.e. MAP kinases), which are activated by 5-HT suggesting neuromodulatory function.