Cytokine-targeted therapy for the management of solid organ transplant recipients

Szczepanik, Amanda; Iasella, Carlo J.; McDyer, John F.; Ensor, Christopher R.

doi:10.1016/j.humimm.2018.12.006

Cited by 5 publications

(5 citation statements)

References 65 publications

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“…First, we focused our analysis on two immunological mediators which have a common double advantage: to be extremely relevant for the immune response after transplantation and to be the target of drugs already available on the market (i.e., Tocilizumab, Sarilumab) or in advanced experimental clinical phases in humans (i.e., Eldelumab). IL-6 is critical for the progression of naïve B cells transforming into plasmablasts and mature plasma cells as well as shaping T cell immunity and is also responsible for activating the production of IL-17 signalling, inhibiting Treg function 44 . The chemokine CXCL10 is a potent chemoattractant for macrophages, dendritic cells, NK cells, and activated T cell and its level rapidly rises following organ reperfusion and during early rejection of the heart, kidney and liver 45 .…”

Section: Discussionmentioning

confidence: 99%

Circulating CXCL10 and IL-6 in solid organ donors after brain death predict graft outcomes

Piemonti

Sordi

Pellegrini

et al. 2021

Sci Rep

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We tested the hypothesis that circulating CXCL10 and IL-6 in donor after brain death provide independent additional predictors of graft outcome. From January 1, 2010 to June 30, 2012 all donors after brain death managed by the NITp (n = 1100) were prospectively included in this study. CXCL10 and IL-6 were measured on serum collected for the crossmatch at the beginning of the observation period. Graft outcome in recipients who received kidney (n = 1325, follow-up 4.9 years), liver (n = 815, follow-up 4.3 years) and heart (n = 272, follow-up 5 years) was evaluated. Both CXCL-10 and IL-6 showed increased concentration in donors after brain death. The intensive care unit stay, the hemodynamic instability, the cause of death, the presence of risk factors for cardiovascular disease and the presence of ongoing infection resulted as significant determinants of IL-6 and CXCL10 donor concentrations. Both cytokines resulted as independent predictors of Immediate Graft Function. Donor IL-6 or CXCL10 were associated with graft failure after liver transplant, and acted as predictors of recipient survival after kidney, liver and heart transplantation. Serum donor IL-6 and CXCL10 concentration can provide independent incremental prediction of graft outcome among recipients followed according to standard clinical practice.

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Section: Discussionmentioning

confidence: 99%

Circulating CXCL10 and IL-6 in solid organ donors after brain death predict graft outcomes

Piemonti

Sordi

Pellegrini

et al. 2021

Sci Rep

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“…For instances, IL-12/IL-23 inhibitors ustekinumab and briakinumab have been studied in patients with psoriasis, psoriatic arthritis, and Crohn’s disease, with cellulitis being the most reported serious infection. 22 Several studies showed a beneficial effect of IL-1β blockade by canakinumab, which led to a reduction in neutrophilic inflammation in the graft. 23,24 IL-17A antagonists such as secukinumab or ixekizumab may prevent allorecognition of the donor allograft and the mounting of immune response against the allograft.…”

Section: Cytokinesmentioning

confidence: 99%

Novel Soluble Mediators of Innate Immune System Activation in Solid Allograft Rejection

et al. 2021

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During the past years, solid allograft rejection has been considered the consequence of either cellular-or antibody-mediated reaction both being part of the adaptive immune response, whereas the role of innate immunity has been mostly considered less relevant. Recently, a large body of evidence suggested that the innate immune response and its soluble mediators may play a more important role during solid allograft rejection than originally thought. This review will highlight the role of novel soluble mediators that are involved in the activation of innate immunity during alloimmune response and solid allograft rejection. We will also discuss emerging strategies to alleviate the aforementioned events. Hence, novel, feasible, and safe clinical therapies are needed to prevent allograft loss in solid organ transplantation. Fully understanding the role of soluble mediators of innate immune system activation may help to mitigate solid allograft rejection and improve transplanted recipients' outcomes.

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“…Although immunosuppressive drugs such as tacrolimus and mycophenolate mofetil, and corticosteroids allow allografts, drug adverse effects and acute-on-chronic or persistent low-grade rejection remain problematic. 1,2 The innate responses mediated by T, natural killer (NK), or other cell types and involvement of IFN-stimulated genes in allograft rejection is well-accepted. However, the critical drivers of tissue injury in allogeneic settings remain unclear.…”

mentioning

confidence: 99%

“…2 Remarkably, gene expression profiling indicates that acute and chronic rejection share similarities in activation of IFN-g, TNF-a, or other cytokines, chemokines, and receptors. 2,3 To control lymphocyte-dependent allograft rejection, therapeutic targets include ILs (eg, IL-2, -4, -6, -12/ 23, and -15) 1,4 and chemokines, 5 whereas controlling innate responses needs additional strategies. 6 Transplanting allogeneic cells or tissues is highly significant for liver-directed therapies.…”

mentioning

confidence: 99%

Tumor Necrosis Factor Directs Allograft-Related Innate Responses and Its Neutralization Improves Hepatocyte Engraftment in Rats

Jaber

Sharma

Mui

et al. 2021

The American Journal of Pathology

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Cytokine-targeted therapy for the management of solid organ transplant recipients

Cited by 5 publications

References 65 publications

Circulating CXCL10 and IL-6 in solid organ donors after brain death predict graft outcomes

Circulating CXCL10 and IL-6 in solid organ donors after brain death predict graft outcomes

Novel Soluble Mediators of Innate Immune System Activation in Solid Allograft Rejection

Tumor Necrosis Factor Directs Allograft-Related Innate Responses and Its Neutralization Improves Hepatocyte Engraftment in Rats

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