Prolactin Induces IL-2 Associated TRAIL Expression on Natural Killer Cells from Chronic Hepatitis C Patients In vivo and In vitro

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Author(s): Maria Luisa Hernández Medel, Gabriela Gutierrez Reyes, Luz Marina Porras, Arturo Reding Bernal, Jesús Serrano Luna, Adolfo Perez Garcia, Jacqueline Cordova, Adalberto Parra, Srinivas Mummidi, David Kershenobich, Joselín Hernández*.

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets

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Background: Natural killer cells (NKC) are a major component of 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 NKC.

Objective: To explore if hyperprolactinemia can activate NKC in HCVp.

Method: 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 controls.

Results: 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 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, increase in TRAIL and IL-2 were associated with viral load decrease. This treatment could potentially be used to reactivate NKC in HCVp.

Keywords: HCV, TRAIL, NKG2D, Viral load response, IFN-γ, hyperprolactinemia.

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(E-pub Ahead of Print)
DOI: 10.2174/1871530319666181206125545
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