Submit Manuscript  

Article Details


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

[ Vol. 19 , Issue. 7 ]

Author(s):

Maria L.H. Medel, Gabriela G. Reyes, Luz M. Porras, Arturo R. Bernal, Jesús S. Luna, Adolfo P. Garcia, Jacqueline Cordova, Adalberto Parra, Srinivas Mummidi, David Kershenobich and Joselín Hernández*   Pages 975 - 984 ( 10 )

Abstract:


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 NKC.

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 controls.

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.

Keywords:

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

Affiliation:

Infectology Service, General Hospital of Mexico Dr. "Eduardo Liceaga", Mexico City, Liver, Pancreas and Motility Laboratory (HIPAM) - Experimental Medicine Research Unit, Faculty of Medicine, Mexico City, Liver, Pancreas and Motility Laboratory (HIPAM) - Experimental Medicine Research Unit, Faculty of Medicine, Mexico City, Directorate of Research, General Hospital of Mexico Dr. Eduardo Liceaga ”, Mexico City, Department of Cell Biology, IPN Research and Advanced Studies Center, Mexico City, Liver, Pancreas and Motility Laboratory (HIPAM) - Experimental Medicine Research Unit, Faculty of Medicine, Mexico City, Directorate of Research, General Hospital of Mexico Dr. Eduardo Liceaga ”, Mexico City, Department of Endocrinology, National Institute of Perinatology “Isidro Espinosa de los Reyes ”, Mexico City, South Texas Diabetes & Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Edinburg, Texas, National Institute of Medical Sciences and Nutrition “Salvador Zubirán”, Mexico City, Liver, Pancreas and Motility Laboratory (HIPAM) - Experimental Medicine Research Unit, Faculty of Medicine, Mexico City

Graphical Abstract:



Read Full-Text article