Das immunsuppressive Potential von Dopaminrezeptoragonisten

Dopamine receptor agonists (DAs) are increasingly used in chronic diseases of the nervous system, above all Parkinson’s disease. Nevertheless, the known immunosuppressive potential of the DAs has had little influence on the clinical use of these drugs. In vitro experiments, experiences in animal models and pilot experiments with patients suffering from autoimmune diseases like rheumatoid arthritis point towards a clinical noticeable immunemodulatory potential of DAs. In this study we compared the influence of the ergot-derived DAs bromocriptine (BCT) and pergolide (PGL) and the non-ergot DA pramipexole (PPX) on lymphocyte culture in vitro and in vivo in a murine relapsing experimental autoimmune encephalomyelitis (EAE) in SJL mice, a prototypic animal model for multiple sclerosis. We could show that the DAs BCT and PGL have dose related immunosuppressive qualities. EAE was markedly suppressed with once daily doses of 20 mg/kg BCT. By the contrast biologically equivalent doses of PGL (5 mg/kg) or PPX (4 mg/kg) did not lead to a significant reduction of EAE. Only when PGL was increased to 20 mg/kg EAE was significantly reduced. Treatment effect was correlated with suppression of prolactin serum levels. In vitro, the 3 DAs had only minor effects at high concentrations (10µM) on lymphocyte proliferation and cytokine production. Because no D2-4- and very few D1-like dopamine receptors have been detectable on our cells, we think that the effects of the DAs BCT (D2) and PGL (D2>D3, and D1) cannot be explained by direct interaction with dopamine receptors on lymphocytes. The prolactin suppression by DAs should be regarded as the main reason for the beneficial effect of DAs in this animal model. The immunosuppressive potential of DAs should be further investigated in autoimmune diseases like multiple sclerosis. Attention should be paid to possible immunosuppressive side effects for example in patients with movement disorders who have to be treated for many years with DAs.