Differential Effect of Mixed D1/D2and Selective D2Dopaminergic Antagonists on Mouse T and B Lymphocyte Proliferation and Interleukin Production In Vitro

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Abstract
The effects of some dopaminergic antagonists were investigated on mouse lymphocyte proliferative responses in vitro. The mixed D1/D2 dopaminergic antagonists chlorpromazine, haloperidol and fIupentixol inhibited 3H-Thymidine incorporation into adult BALB/c mouse spleen cells stimulated by concanavalin A, lipopolysaccharide from Escherichia coli, and allogenic cells in a mixed lymphocyte reaction. The inhibition was achieved at concentrations greater than 10−6M. It was not accounted for by decreased cell viability and it was no longer demonstrable when the compound was added 24h or 48h after the mitogenic stimulus. Conversely selective D2 dopaminergic antagonists sulpiride, metoclopramide and domperidone had no inhibitory effect at concentrations ranging from 10−9 to 10−5 or 10−4M. The three mixed Dl/D2 antagonists inhibited the mitogenic effect of interleukin-1 on concanavalin A-stimulated thymocytes, but not the activity of interleukin-2 on the proliferaiton of the CTLL-2 cell line. The mixed Dl/D2 antagonists interfered with the production of interleukin-2 but not with that of interleukin-1. These results indicate that dopaminergic antagonists may differerentially affect lymphocyte proliferative responses to T or B cell mitogens or alloantigens. The mechanisms involved in terms of receptor specific or non specific phenomenons are discussed.