Central catecholamine depleton inhibits peripheral lymphocyte proliferation and splenocyte cytokine production
Duisburg-Essen (2004), 61 Bl.
Dissertation / Fach: Medizin
Medizinische Fakultät » Universitätsklinikum Essen » Institut für Medizinische Psychologie und Verhaltensimmunbiologie
Schedlowski, Manfred (Doktorvater, Betreuerin)
Brodde, Otto-Erich (GutachterIn)
Evidence demonstrating that immune response is under the control of central nervous system has been accumulated during the past two decades. Central catecholamines have been proved to play a pivotal role in modulation of humoral and cellular immunity both in vitro and in vivo. However, the modulation of central catecholamine depletion on peripheral cellular immune response remains somewhat unclear. Therefore, we designed a set of experiments to analyse the influence of central catecholamine depletion by i.c.v. 6-OHDA injection on peripheral cellular immune functions. Two, four and seven days after the injection in rats, they were sacrificed and spleen and blood samples were collected to measure the lymphocyte proliferation, cytokine production and IL-2 mRNA expression. Brain and spleen samples were obtained for catecholamine determination as well. Our data demonstrate that two, four and seven days after i.c.v. 6-OHDA treatment, dopamine, norepinephrine and epinephrine levels in the hypothalamus and in the cortex are significantly reduced. Additionally, norepinephrine and epinephrine concentrations in the spleen are significantly decreased four days after the injection. In contrast, the serotonin levels in the brain and in the spleen are not changed seven days after the central 6-OHDA treatment. More importantly, Con A-induced lymphocyte proliferation and splenocyte cytokine production at both protein (IL-2 and IFN-?) and mRNA (IL-2) levels are significantly reduced seven days after i.c.v. 6-OHDA injection. These results confirm the important role of central catecholamines in modulating peripheral cellular immune response. Although the precise mechanism of how central catecholamine depletion alters peripheral cellular immunity is still not clear, the fact that a significant reduction in splenic catecholamine contents is observed four days after i.c.v. 6-OHDA treatment suggests that peripheral sympathetic nervous system plays a role in these effects.