Immunomodulatory effects of vasoactive catecholamines

The immunological side effects of catecholamines have recently gained specific attention in the area of sepsis related research, since stimulation of adrenergic and dopaminergic receptors can lead to a modulation of the cytokine network. Catecholamines alter the production of these immune mediators in peripheral blood cells but also in various tissues such as liver, spleen, lung, heart, kidney and the skin. The sympathetic regulation of cytokines is highly dependent on which type of receptor is stimulated. Whereas ligation of the alpha-adrenoreceptor is associated with predominantly immunostimulating effects (i.e. the induction of TNF alpha and IL-1 beta), stimulation of the beta-adrenoreceptor usually has immunosuppressive consequences (i.e. inhibition of TNF alpha and IL-1 beta, induction of IL-10). In case both receptors are stimulated (i.e. by epinephrine) the beta-adrenoreceptor mediated effects usually dominate those induced by alpha-adrenoreceptor stimulation. Moreover, the adrenergic immunostimulation can be differentially regulated depending on which type of cell or tissue is stimulated. This suggests locoregional effects. Dopaminergic immunomodulation is dominated by immunosuppressive effects, such as the induction of IL-6, the inhibition of TNF alpha, the attenuation of the chemoattractant effect of IL-8 and the inhibition of endothelial adhesion. Catecholamines also alter the number and function of neutrophils and lymphocytes. This again depends on which type of receptor is stimulated. Whereas beta-adrenergic stimulation leads to lymphocytosis, alpha-adrenoreceptors mediate lymphocyte homing. Catecholamine induced neutrophilia involves alpha 1-adrenoreceptor ligation. With respect to neutrophil function, epinephrine increases the respiratory burst. Up to now, most of the available data on catecholamine-induced immunomodulation were obtained in experimental settings. The overwhelming, clear results indicate that this system might have important implications for the pathophysiology of immunological diseases such as septic shock, which are accompanied by increased levels of catecholamines.