Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Dirks, M; Pflugrad, H; Tryc, AB; Schrader, AK; Ding, X; Lanfermann, H; Jäckel, E; Schrem, H; Beneke, J; Barg-Hock, H; Klempnauer, J; Falk, CS; Weissenborn, K.
Impact of immunosuppressive therapy on brain derived cytokines after liver transplantation.
Transpl Immunol. 2020; 58:101248
Doi: 10.1016/j.trim.2019.101248
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Schrem Harald Heinrich
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Aged - administration & dosage
- Brain - metabolism
- Brain-Derived Neurotrophic Factor - blood
- Calcineurin Inhibitors - adverse effects, therapeutic use
- Cell Self Renewal - administration & dosage
- Cohort Studies - administration & dosage
- Female - administration & dosage
- Gene Expression Regulation - administration & dosage
- Humans - administration & dosage
- Immunosuppression - administration & dosage
- Interferon-gamma - blood
- Liver Transplantation - administration & dosage
- Male - administration & dosage
- Middle Aged - administration & dosage
- Neuroimmunomodulation - drug effects
- Neuronal Plasticity - administration & dosage
- Platelet-Derived Growth Factor - metabolism
- T-Lymphocytes - metabolism
- Find related publications in this database (Keywords)
- Immunosuppression
- Brain derived cytokines
- Cognitive function
- Brain
- Imaging