2011; 32(2): 176-186
PubMed PMID: 21552197
Adult, Animals, Brain:drug effects, Cells, Cultured, Clozapine:pharmacology, Dopamine:pharmacology, Dopamine Antagonists:pharmacology, Dose-Response Relationship, Drug, Female, Haloperidol:pharmacology, Humans, Interferon-gamma:metabolism, Interleukin-10:.
OBJECTIVES: Dopamine (DA) administration in sepsis is used to modulate the hypotensive condition and to normalize the blood vessels perfusion. However, whether this administration of DA has an effect on the release of cytokines in vivo deserves investigation.
METHODS AND RESULTS: Pre-exposure of DA (1 µg/ml) to whole blood enhanced IL-10 (30%) production level following LPS stimulation. This IL-10 enhancement became statistically significant (p<0.001) upon the addition of D2-DA receptor (DAR) antagonists, Clozapine or Haloperidol. Furthermore, systemic administration of DA (0.5-50 mg/kg) in mice suppressed significantly LPS-induced TNF-α levels in blood, liver, spleen, brain, and lungs; IL-10 levels in blood, brain and liver; and IFN-γ levels in blood, liver, brain, and lungs. On the other hand, DA enhanced significantly LPS-induced IL-10 production in the lungs and spleen, and IFN-γ levels in the spleen. Administration of Clozapine (54 mg/kg) or Haloperidol (62 mg/kg) with LPS (1 µg) and DA (5 mg/kg) reversed DA suppressive effects on LPS-induced cytokines in blood, IFN-γ in brain and lungs, and enhanced significantly LPS-induced IL-10 production in blood, spleen, liver, and lungs.
CONCLUSIONS: These results indicate that DA modulatory effect on LPS-induced blood cytokines-producing cells is mediated mainly by D2-DAR (D2/ D3/D4) through enhancing immune cells migration and extravasation into tissues. Furthermore, DA selectivity on cytokines modulation is tissue specific, mediated by the type of DAR expressed and on the immune cells lodged in each tissue....