Cytokines in Liver Transplantation

Assadiasl, Sara; Mooney, Nuala; Nicknam, Mohammad Hossein

doi:10.1016/j.cyto.2021.155705

Cited by 9 publications

(6 citation statements)

References 123 publications

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“…Moreover, cytokines associated with rejection were also affected by CAP treatment. Metronomic CAP significantly reduced the levels of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-2, and IL-12p70), which are mainly secreted by immune cells and contributing to rejection[ 47 - 50 ].…”

Section: Discussionmentioning

confidence: 99%

Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients’ T cell ferroptosis

Wang¹,

Wang²,

Zhang³

et al. 2023

World J Gastroenterol

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BACKGROUND Capecitabine (CAP) is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation (LT) in clinical studies. Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice. Ferroptosis, a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation, is an important mechanism by which CAP induces cell death. Therefore, ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after trans-plantation. AIM To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP. METHODS A rat LT model of acute rejection was established, and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT. In vitro , primary CD3 + T cells were sorted from rat spleens and human peripheral blood, and co-cultured with or without 5-fluorouracil (5-FU) (active agent of CAP). The levels of ferroptosis-related proteins, ferrous ion concentration, and oxidative stress-related indicators were observed. The changes in mito-chondrial structure were observed using electron microscopy. RESULTS With no significant myelotoxicity, metronomic CAP alleviated graft injury (Banff score 9 vs 7.333, P < 0.001), prolonged the survival time of the recipient rats (11.5 d vs 16 d, P < 0.01), and reduced the infiltration rate of CD3 + T cells in peripheral blood (6.859 vs 3.735, P < 0.001), liver graft (7.459 vs 3.432, P < 0.001), and spleen (26.92 vs 12.9, P < 0.001), thereby inhibiting acute rejection after LT. In vitro , 5-FU, an end product of CAP metabolism, induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4, which caused the accumulation of ferrous ions. It also inhibited nuclear erythroid 2 p45-related factor 2, heme oxygenase-1, and glutathione peroxidase 4, eventually leading to oxidative damage and ferroptosis of T cells. CONCLUSION Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3 + T cell ferroptosis, which makes it an effective immunosuppressive agent after LT.

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Section: Discussionmentioning

confidence: 99%

Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients’ T cell ferroptosis

Wang¹,

Wang²,

Zhang³

et al. 2023

World J Gastroenterol

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“…The JAK inhibitors are a new group of immunomodulatory agents that have been approved to treat certain rheumatologic, allergic, and severe infectious diseases 20 ; however, their effect on allograft survival has not yet been elucidated. The implication of cytokines has been demonstrated in various phases of solid organ transplantation, including donor selection, perioperative complications, IRI, early graft dysfunction, acute rejection, and chronic allograft dysfunction 59,75,76 . Given that the JAK/STAT pathway is involved in the signal transduction of most cytokines, it is conceivable that JAK inhibition could prevent or attenuate some adverse effects of alloimmune responses in patients.…”

Section: Discussionmentioning

confidence: 99%

“…The implication of cytokines has been demonstrated in various phases of solid organ transplantation, including donor selection, perioperative complications, IRI, early graft dysfunction, acute rejection, and chronic allograft dysfunction. 59,75,76 Given that the JAK/STAT pathway is involved in the signal transduction of most cytokines, it is conceivable that JAK inhibition could prevent or attenuate some adverse effects of alloimmune responses in patients. Hence, there have been some efforts to apply JAK inhibitors to regulate alloimmune responses, particularly in renal transplantation.…”

Section: Discussionmentioning

confidence: 99%

JAK Inhibitors in Solid Organ Transplantation

Assadiasl

Mojtahedi

Nicknam

2023

The Journal of Clinical Pharma

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Janus kinase (JAK) inhibitors are a novel group of immunosuppressive drugs approved to treat certain rheumatic and allergic disorders; however, their efficacy in the regulation of alloimmune responses after solid organ transplantation has not yet been elucidated. In the present review, we have summarized the results of in vitro, in vivo, experimental, and clinical trial studies about the efficacy and safety of JAK inhibitors in improving allograft survival in solid organ transplantations, including kidney, heart, lung, and liver transplants. Moreover, reports on administering JAK inhibitors to steroid‐resistant patients with graft versus host disease (GvHD) after solid organ transplantation have been reviewed. Overall findings are suggestive of a beneficial role for JAK inhibitors in organ transplantation: for example, they have been shown to improve allograft function, reduce the rate and score of acute rejection, downregulate the expression of proinflammatory cytokines and adhesion molecules, and decrease oxidative stress. However, the adverse effects of these drugs, in particular bone marrow suppression and infection, remain an obstacle.

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“…Вони вивільняються після будь-якого пошкодження тканин і відіграють важливу роль у захисних механізмах, загоєнні ран та розвитку посттравматичного болю [1,3].…”

Section: вступunclassified

The Influence of Adjuvants on the Expression of Pro-Inflammatory Cytokines During Spinal Anesthesia

Shchegolkov

2024

Act. Probl. of the Modern Med.

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Objective. To investigate the influence of adjuvants (fentanyl and dexmedetomidine) on TNF-α and IL-6 expression during spinal anesthesia based on bupivacaine. Materials and Methods. A total of 150 patients with an average age of 41.3±8.2 years undergoing endoscopic biportal discectomy were examined. Patients were divided into groups: Group 1 received intrathecally 2.5 ml hyperbaric bupivacaine; Group 2 received intrathecally 2.5 ml hyperbaric bupivacaine and 25 μg fentanyl; Group 3 received intrathecally 2.5 ml hyperbaric bupivacaine and 5 μg dexmedetomidine. Peripheral venous blood was collected 1 hour before surgery, at 12 and 24 hours postoperatively, to measure TNF-α and IL-6 levels through solid-phase enzyme-linked immunosorbent assay. Results. The expression of pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)) may play a crucial role in modulating postoperative inflammatory reactions. However, contemporary scientific literature presents conflicting data on the influence of anesthetics on cytokine release. Groups 1 and 2 showed a significant increase in TNF-α levels at all observation stages. In Group 3, a significant elevation in TNF-α was observed only 12 hours postoperatively, with no statistically significant difference in the subsequent 24 hours. Inter-group analysis of TNF-α dynamics revealed the smallest increase in Group 3, while Group 1 had significantly higher values compared to Group 3 and Group 2. In all study groups, there was a progressive, statistically significant increase in IL-6 levels within 24 hours postoperatively. However, Group 1 exhibited consistently higher values, with statistically significant differences compared to Group 2 and Group 3. In Groups 2 and 3, statistically significant inter-group differences in IL-6 were noted 12 hours postoperatively, but there was no statistical significance in IL-6 dynamics 24 hours postoperatively. Conclusion. Intrathecal use of bupivacaine with dexmedetomidine had a lesser impact on postoperative TNF-α and IL-6 expression during endoscopic biportal discectomy.

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Cytokines in Liver Transplantation

Cited by 9 publications

References 123 publications

Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients’ T cell ferroptosis

Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients’ T cell ferroptosis

JAK Inhibitors in Solid Organ Transplantation

The Influence of Adjuvants on the Expression of Pro-Inflammatory Cytokines During Spinal Anesthesia

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