Nuclear factor-kappa B is involved in the catecholaminergic suppression of immunocompetent cells

Catecholamines are known to exert a powerful impact on the immune system by downregulation of proliferation and differentiation, and induction of apoptosis. However, the mechanism for this regulatory route is still unclear. Therefore well established human monocytic cell-lines and nontransformed human monocytes, obtained from peripheral blood, were incubated with an optimal concentration of LPS and varying concentrations of the catecholamine dopamine. The proliferative response to LPS was determined by [3H]thymidine incorporation, and a significant suppressive effect by dopamine was obtained. LPS-induced binding of NF-kappa B to DNA, determined by electrophoretic mobility shift assay, was inhibited by extrinsic dopamine, leading to a decreased proliferation and cytokine expression. In contrast, the intracellular ceramide concentration was not affected by incubation of peripheral blood lymphocytes with dopamine. Our findings suggest that the NF-kappa B-I-kappa B transcription machinery may well be involved in the catecholaminergic regulation of the immune system, while the ceramide-SAPK/JNK cascade appears not to play a significant role in this suppression.