Dopamine regulates cytokine secretion during innate and adaptive immune responses

Dopamine (DA) is synthesized by various immune cells. DA receptors (DARs), which comprise five isoforms, are expressed on the surface of these cells. Therefore, it is likely that DA plays a role in regulating innate and adaptive responses. However, the underlying molecular mechanism(s) is largely unknown. Here, we found that, during innate immune responses, DA suppressed secretion of IFN-gamma, TNF-alpha and IL-1 beta, but promoted secretion of IL-10 and CXCL1 by lipopolysaccharide (LPS)-stimulated mouse splenocytes, suggesting that DA regulates cytokine secretion. Immune subset studies indicated that DA suppressed secretion of IFN-gamma, TNF-alpha and IL-1 beta by NK cells, as well as secretion of TNF-alpha by neutrophils and monocytes; however, DA up-regulated IL-10 secretion by neutrophils, monocytes, B cells, macrophages (M phi s) and dendritic cells within the splenocyte population. In addition, DA up-regulated secretion of CXCL1 by LPS-stimulated NK cells and M phi s. Meanwhile, treatment with DAR agonists or antagonists suppressed secretion of inflammatory cytokines from LPS-stimulated splenocytes. Pre-treatment of LPS-stimulated splenocytes with the PI3K inhibitor wortmannin reversed DA-mediated suppression of IFN-gamma secretion, indicating that DA regulates IFN-gamma secretion via the inositol 1,4,5-trisphosphate signaling pathway in these cells. Administration of DA and LPS to mice immunized with chicken ovalbumin (OVA) increased secretion of IL-5 by mouse lung lymphocytes, suggesting that DA promotes OVA-specific T(h)2-mediated immune responses by these cells. Taken together, these findings indicate that DA regulates cytokine secretion during innate and adaptive immune responses.