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

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 flupentixol 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(-6) M. It was not accounted for by decreased cell viability and it was no longer demonstrable when the compound was added 24 h or 48 h 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(-4) M. The three mixed D1/D2 antagonists inhibited the mitogenic effect of interleukin-1 on concanavalin A-stimulated thymocytes, but not the activity of interleukin-2 on the proliferation of the CTLL-2 cell line. The mixed D1/D2 antagonists interfered with the production of interleukin-2 but not with that of interleukin-1. These results indicate that dopaminergic antagonists may differentially 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.