Objective: Besides its effects as a neurotransmitter, dopamine also influences the immune system. In the neurological context, it has already been described that the dopaminergic pathway shows sex-specific differences regarding dopamine release and dopamine receptor expression. However, whether dopamine affects the peripheral immune system in a sex-specific manner has little been studied yet. Gaining knowledge in this area could be beneficial for the treatment of immune system defects like autoimmune diseases.
Methods: Blood was collected from healthy men and women (n=12) and PBMCs were isolated. In vitro stimulations of mixed PBMCs were performed using a D₁- or D₂-like agonist together with CpG ODN2006. After 24h of stimulation, activation marker expression was analysed via flow cytometry and cytokine secretion via Legendplex. All subjects gave written consent to the study.
Results: Dopaminergic stimulation together with B cell-specific activator CpG ODN2006 increases CD71 and decreases HLA-DR expression on B cells from both women and men pointing to a B cell activation, but with reduced ability of antigen presentation in both sexes. Meanwhile, monocytes from women show increased activation via upregulation of CD86 and HLA-DR while downregulated activation marker expression is observed in men. These findings are consistent with cytokine secretion: IL1b, MCP1, IL6 and IL18 are upregulated via dopaminergic stimulation in women and downregulated in men.
Conclusion: While dopaminergic stimulation of mixed PBMCs shifts the B cells to an activated state for both sexes, monocytes show proinflammatory responses in women and antiinflammatory responses in men. Thus, sex should be considered as an influencing factor in the context of neuro-immune interactions. Whether the observed sex-specific response of monocytes is indirectly controlled by interaction with activated B cells or by dopamine alone must be analysed in further studies. The underlying mechanism causing these sex-specific differences also remains to be clarified.