In vivo Effects of Acute Inflammatory Responses on Dopaminergic Receptor Expression in Leukocytes and Marginal Effects of Hypoxia Pretreatment.

INTRODUCTION: Lipopolysaccharide (LPS) is widely used to study the mechanisms underlying acute inflammation. Interestingly, several studies suggest that LPS also regulates central dopaminergic signaling. Despite these findings in the brain, the effects of LPS on the dopaminergic system in the periphery remain poorly understood. Notably, peripheral immune cells express dopamine receptors (DRs) and can respond to dopamine. Dysregulation of the dopaminergic system in immune cells has been reported in various chronic inflammatory conditions. Additionally, studies suggest that hypoxia may also modulate dopamine synthesis and potentially amplify LPS-induced effects. METHODS: The aim of this study was to investigate the effects of peripheral LPS administration on the dopaminergic system in male human peripheral blood mononuclear cells by measuring dopamine plasma levels and the expression of tyrosine hydroxylase and DRs. Additionally, we explored whether these effects are modulated by prior hypoxic exposure. RESULTS: Our results suggest that in vivo LPS modulates the expression of DRs on monocytes and natural killer cells, as reflected by an upregulation after 24 h. In contrast, the effects of LPS on T and B cells were weaker, with a predominantly inhibitory influence on DR expression, supporting the notion of a cell-specific effect of LPS on dopaminergic signaling within the immune system. Additionally, our results indicate that hypoxic pretreatment did not alter LPS-induced changes in the dopaminergic pathway. CONCLUSION: Taken together, this study demonstrates for the first time that systemic LPS administration modulates DR expression in male peripheral immune cells. Further, our in vitro findings suggest that it is the LPS-induced immune response, rather than LPS itself, that drives changes in the dopaminergic pathway in specific immune cell subpopulations. However, further research is needed to elucidate the functional relevance of these findings in clinical contexts.