Immunosuppression for lung transplantation

Allan, James S.

doi:10.1053/j.semtcvs.2004.09.010

Cited by 6 publications

(4 citation statements)

References 96 publications

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“…Five-year survival in the alemtuzumab group was 50%, which is comparable to the 5-year survival reported by the 2011 ISHLT registry of 53% [Christie 2011]. We believe these are important findings because higher immunosuppressive doses and levels have been shown to correlate with increasing morbidity and mortality [Allan 2004].…”

Section: E256supporting

confidence: 70%

Long-Term Outcomes following Alemtuzumab Induction in Lung Transplantation

Wehman¹,

Griffith²,

Balwan³

et al. 2013

HSF

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Section: E256supporting

confidence: 70%

Long-Term Outcomes following Alemtuzumab Induction in Lung Transplantation

Wehman¹,

Griffith²,

Balwan³

et al. 2013

HSF

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“…We demonstrated using well-defined in vitro assays that the addition of specific immunosuppressive drugs differentially impacted on NK cell cytotoxicity, cytokine production and proliferation, which was dependent on the primary stimulus. Importantly, these immunosuppressive drugs were found to impair NK cell function at concentrations corresponding to the therapeutic range used in the management of lung transplant patients [9], [10], [21], [22], [23].…”

Section: Discussionmentioning

confidence: 99%

“…Anti-proliferative agents including Azathioprine and Mycophenolate mofetil (MMF) impede lymphocyte growth and expansion. The anti-metabolite MMF is rapidly converted into its active form of Mycophenolic acid (MPA) after administration which then inhibits the enzyme, inosine monophosphate dehydrogenase, involved in de novo purine synthesis resulting in diminished lymphocyte proliferation [9], [10], [11]. Corticosteroids, such as Prednisolone, bind with glucocorticoid receptors, forming a complex which interacts with cellular DNA in the nucleus to modify gene transcription.…”

Section: Introductionmentioning

confidence: 99%

Impact of Commonly Used Transplant Immunosuppressive Drugs on Human NK Cell Function Is Dependent upon Stimulation Condition

et al. 2013

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Lung transplantation is a recognised treatment for patients with end stage pulmonary disease. Transplant recipients receive life-long administration of immunosuppressive drugs that target T cell mediated graft rejection. However little is known of the impact on NK cells, which have the potential to be alloreactive in response to HLA-mismatched ligands on the lung allograft and in doing so, may impact negatively on allograft survival. NK cells from 20 healthy controls were assessed in response to Cyclosporine A, Mycophenolic acid (MPA; active form of Mycophenolate mofetil) and Prednisolone at a range of concentrations. The impact of these clinically used immunosuppressive drugs on cytotoxicity (measured by CD107a expression), IFN-γ production and CFSE proliferation was assessed in response to various stimuli including MHC class-I negative cell lines, IL-2/IL-12 cytokines and PMA/Ionomycin. Treatment with MPA and Prednisolone revealed significantly reduced CD107a expression in response to cell line stimulation. In comparison, addition of MPA and Cyclosporine A displayed reduced CD107a expression and IFN-γ production following PMA/Ionomycin stimulation. Diminished proliferation was observed in response to treatment with each drug. Additional functional inhibitors (LY294002, PD98059, Rottlerin, Rapamycin) were used to elucidate intracellular pathways of NK cell activation in response to stimulation with K562 or PMA-I. CD107a expression was significantly decreased with the addition of PD98059 following K562 stimulation. Similarly, CD107a expression significantly decreased following PMA-I stimulation with the addition of LY294002, PD98059 and Rottlerin. Ten lung transplant patients, not receiving immunosuppressive drugs pre-transplant, were assessed for longitudinal changes post-transplant in relation to the administration of immunosuppressive drugs. Individual patient dynamics revealed different longitudinal patterns of NK cell function post-transplantation. These results provide mechanistic insights into pathways of NK cell activation and show commonly administered transplant immunosuppression agents and clinical rejection/infection events have differential effects on NK cell function that may impact the immune response following lung transplantation.

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“…CsA was approved by the FDA in 1983. It is a cyclic polypeptide, derived from the fungus Tolypocladium inflatum [43]. Tacrolimus (also known as FK506), used since 1995, is a macrolide antibiotic, isolated from the soil bacterium Streptomyces tsukabensis, with quite a similar mechanism of action as CsA [44], which will be discussed later.…”

Section: Two Calcineurin Inhibitors In Clinical Usementioning

confidence: 99%

Transplant Drugs against SARS, MERS and COVID-19

et al. 2020

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There is an urgent need to develop drugs and vaccines to counteract the effects of the new coronavirus SARS-CoV-2 and adequately treat the corona virus disease (COVID-19). As these drugs are still under investigation, research also focuses on existing medication with proven effectiveness in other coronaviral diseases. The advantages of existing therapeutic drugs that are currently approved (for other indications) are the known safety profile, general availability and relatively lower costs involved in extending the purpose to a new disease. Calcineurin inhibitors (CNI) are drugs that have shown effectiveness in several coronaviral diseases, and are well-known and widely used drugs in transplant medicine. The aim of this narrative review is to present the current evidence of CNI in coronaviral diseases, the biophysiology of CNI and to suggest possible ways to study CNI as a new treatment option for COVID-19. We searched original papers, observational studies, case reports, and meta-analyses published between 2000 and 2020 in English in the PubMed database and Google Scholar using the keywords: (coronavirus), (treatment), (MERS), (SARS), (COVID-19), (tacrolimus), (ciclosporin), (cyclosporin) AND (calcineurin inhibitor). We excluded studies in patients with clear indications for immunosuppressive therapy. Additionally, we searched in the preprint servers and the World Health Organization bulletin. Ten studies were identified and included. Calcineurin inhibitor therapy has been suggested to be effective for coronaviral diseases in different settings. The results are summarized in a table. CNI should be investigated as a first treatment option based on evidence of direct antiviral effects and its properties preventing severe systemic hyperinflammation, as has been observed in COVID-19 with predominantly pulmonary immunopathological changes.

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Immunosuppression for lung transplantation

Cited by 6 publications

References 96 publications

Long-Term Outcomes following Alemtuzumab Induction in Lung Transplantation

Long-Term Outcomes following Alemtuzumab Induction in Lung Transplantation

Impact of Commonly Used Transplant Immunosuppressive Drugs on Human NK Cell Function Is Dependent upon Stimulation Condition

Transplant Drugs against SARS, MERS and COVID-19

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