Background: Natural killer cells (NKC) are a major component of the innate immune response
to HCV, mediating their effects through TRAIL and IFN-γ. However, their function is diminished
in chronic HCV patients (HCVp). Prolactin is an immunomodulatory hormone capable of activating
Objective: The study aims to explore if hyperprolactinemia can activate NKC in HCVp.
Methods: We treated twelve chronic HCVp (confidence level =95%, power =80%) for 15 days with
Levosulpiride plus Cimetidine to induce mild hyperprolactinemia. Before and after treatment, we determined
TRAIL and NKG2D expression on peripheral blood NKC, along with cytokine profiles, viral
loads and liver function. We also evaluated in vitro effects of prolactin and/or IL-2 on NKC TRAIL or
NKG2D expression and IFN-γ levels on cultured blood mononuclear cells from 8 HCVp and 7 healthy
Results: The treatment induced mild hyperprolactinemia and increased TRAIL expression on NKC as
well as the secretion of IL-1ra, IL-2, PDGF and IFN-γ. Viral loads decreased in six HCVp. IL-2 and
TRAIL together explained the viral load decrease. In vitro, prolactin plus IL-2 synergized to increase
TRAIL and NKG2D expression on NKC from HCVp but not in controls.
Conclusion: Levosulpiride/Cimetidine treatment induced mild hyperprolactinaemia that was associated
with NKC activation and Th1-type cytokine profile. Also, an increase in TRAIL and IL-2 was associated
with viral load decrease. This treatment could potentially be used to reactivate NKC in HCVp.