Impact of immunosuppressive therapy on brain derived cytokines after liver transplantation.

Autor: Dirks M; Department of Neurology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Centre Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany. Electronic address: dirks.meike@mh-hannover.de., Pflugrad H; Department of Neurology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Centre Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany., Tryc AB; Department of Neurology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Centre Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany., Schrader AK; Department of Neurology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Centre Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany., Ding X; Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Germany., Lanfermann H; Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Germany., Jäckel E; Integrated Research and Treatment Centre Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany., Schrem H; Integrated Research and Treatment Centre Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany; General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany., Beneke J; Integrated Research and Treatment Centre Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany., Barg-Hock H; General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany., Klempnauer J; Integrated Research and Treatment Centre Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany; General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany., Falk CS; Integrated Research and Treatment Centre Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany; Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany., Weissenborn K; Department of Neurology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Centre Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
Jazyk: angličtina
Zdroj: Transplant immunology [Transpl Immunol] 2020 Feb; Vol. 58, pp. 101248. Date of Electronic Publication: 2019 Oct 24.
DOI: 10.1016/j.trim.2019.101248
Abstrakt: Background: While acute neurotoxic side effects of calcineurin inhibitors (CNI) are well-known, data upon long-term effects on brain structure and function are sparse. We hypothesize that long-term CNI therapy affects the neuroimmune system, thereby, increasing the risk of neurodegeneration. Here, we measured the impact of CNI therapy on plasma levels of brain- and T cell-derived cytokines in a cohort of patients after liver transplantation (LT).
Methods: Levels of T cell-mediated cytokines (e.g. Interferon-γ (IFN-γ)) and brain-derived cytokines (e.g. brain derived neurotrophic factor (BDNF), platelet derived growth factor (PDGF)) were measured by multiplex assays in plasma of 82 patients about 10 years after LT (17 with CNI free, 35 with CNI low dose, 30 with standard dose CNI immunosuppression) and 33 healthy controls. Data were related to psychometric test results and parameters of cerebral magnetic resonance imaging.
Results: IFN-γ levels were significantly higher in the CNI free LT patient group (p=0.027) compared to healthy controls. BDNF levels were significantly lower in LT patients treated with CNI (CNI low: p<0.001; CNI standard: p=0.016) compared to controls. PDGF levels were significantly lower in the CNI low dose group (p=0.004) and for PDGF-AB/BB also in the CNI standard dose group (p=0.029) compared to controls. BDNF and PDGF negatively correlated with cognitive function and brain volume (p<0.05) in the CNI low dose group.
Conclusion: Our results imply that long-term treatment with CNI suppresses BDNF and PDGF expression, both crucial for neuronal signaling, cell survival and synaptic plasticity and thereby may lead to cognitive dysfunction and neurodegeneration.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: