A short course of cyclosporine immunosuppression inhibits rejection but not tolerance of rat liver allografts1

Huang, Wen; Yan, Yiqun; Boer, Bastiaan de; Bishop, G. Alex; House, A. K.

doi:10.1097/01.tp.0000044360.20396.ab

Cited by 19 publications

(16 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Circulating and intra-graft levels of pro-inflammatory cytokines, such as IL-6, IL-1β, and TNF-α, are elevated after experimental organ transplantation as well as in clinical studies (Ichikawa et al, 2000). In fact, treatment with immunosuppressive drugs has been shown to prolong allograft survival via the inhibition of pro-inflammatory cytokine expression and production (Murase et al, 1990;Huang et al, 2003). We here found that the expressional levels of these cytokine genes were elevated in transplanted hearts, in which levels were reduced by treatment with db-cAMP.…”

Section: Discussionmentioning

confidence: 99%

Cyclic AMP prolongs graft survival by suppressing apoptosis and inflammatory gene expression in acute cardiac allograft rejection

et al. 2010

View full text Add to dashboard Cite

This study was designed to investigate the effects of cAMP on immune regulation and apoptosis during acute rat cardiac allograft rejection. We found that the production of immune markers such as inflammatory cytokines (IL-1β, IL-6, and TNF-α), iNOS expression, and nitric oxide (NO) production, was significantly increased in the blood and transplanted hearts of allograft recipients, but not of isograft controls. These increases were effectively suppressed by the administration of the membrane permeable cAMP analog dibutyryl cAMP (db-cAMP). Administration of db-cAMP reduced allograft-induced elevation of several biochemical markers, such as adhesion molecule expression, iron-nitrosyl complex formation, caspase-3 activation, and apoptotic DNA fragmentation in an animal model. Furthermore, treatment of allograft recipients with db-cAMP prolonged median graft survival to 11 days compared with a median graft survival time of 8 days in saline-treated allograft recipients. These results suggest that db-cAMP exerts a beneficial effect on murine cardiac allograft survival by modulating allogeneic immune response and cytotoxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Cyclic AMP prolongs graft survival by suppressing apoptosis and inflammatory gene expression in acute cardiac allograft rejection

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The sequences of Taqman primers and probes for rat IL-2, IL-4, IL-10, interferon (IFN)-␥, and glyceraldehyde phosphate dehydrogenase have been reported in previous studies (27,28). Quantification of each cytokine mRNA level was calculated using Sequence Detector version 1.7 software (Applied Biosystems) and a standard curve generated by serial dilutions of a sample with high-level cytokine expression, as previously described (8).…”

Section: Quantification Of Cytokine Mrna Expressionmentioning

confidence: 99%

“…MOPC-21 (Sigma, St. Louis, MO) was used as the negative control antibody. The extent of lobular infiltration by cells staining for R73, CD25, and OX39 was calculated as positive cells per millimeter squared as previously described (8). Deposition of IgG1 and IgM antibodies was scored by a semiquantitative system ranging from 0 (undetectable) to 7 (deposition on 100% of section) (8).…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

“…Cytokine mRNA in liver tissue was measured by quantitative reverse transcriptase-polymerase chain reaction, as described previously (8,27). Total RNA was extracted and reverse transcribed, then diluted cDNA was measured for cytokine gene expression in a quantitative polymerase chain reaction using the ABI PRISM 7700 Sequence Detector (PE Applied Biosystems, Melbourne, Australia).…”

Section: Quantification Of Cytokine Mrna Expressionmentioning

confidence: 99%

“…This has contributed to a view that corticosteroid therapy of liver transplant patients should be minimized or reserved for treatment of rejection episodes (7). Not all immunosuppressive drugs seem to inhibit liver transplant tolerance, and in the same model, cyclosporine (CsA) significantly inhibited rejection but not tolerance (8).…”

mentioning

confidence: 99%

See 2 more Smart Citations

A short course of mycophenolate immunosuppression inhibits rejection, but not tolerance, of rat liver allografts in association with inhibition of interleukin-4 and alloantibody responses

Huang

Yan

et al. 2003

Transplantation

Self Cite

View full text Add to dashboard Cite

show abstract

Revisiting liver transplant immunology: From the concept of immune engagement to the dualistic pathway paradigm

Reding

Davies

2004

Liver Transpl

View full text Add to dashboard Cite

Ever since the demonstration that allografts are rejected through immune reactions of the host, clinical therapies for organ allografts have relied on immune suppression to prevent these destructive events. A growing body of clinical and experimental data suggests that allografts elicit multiple, interactive immune responses. The result is not inevitably graft rejection, and "spontaneous" acceptance of fully allogeneic liver grafts occurs in rodents without immunosuppression. A spectrum of results range from spontaneous acceptance without immunosuppression to rejection with immunosuppression. The "dualistic pathway paradigm" aims to reconcile apparently conflicting observations in liver transplantation and proposes that: (1) immune engagement between the host and the allograft is instrumental in both rejection and acceptance; (2) there exist in all mammalian species congruent interactive pathways of immune activation whereby the fate of the allograft is determined by the quantitative results of these interactions; (3) the dualistic effect of immunosuppressive drugs on pathways of immune activation, conferring the capacity for favorable or unfavorable graft outcome should be investigated in experimental models in which organ allografts are spontaneously accepted. In conclusion the design of clinical strategies based on this research may contribute to protocols resulting in allograft acceptance without chronic immunosuppression. (Liver

show abstract

A short course of cyclosporine immunosuppression inhibits rejection but not tolerance of rat liver allografts1

Abstract: CsA did not significantly inhibit liver transplant acceptance and allowed some activation of T cells and CD25 expression but almost completely inhibited IL-2 and IL-4, which are required for survival of activated T cells.

Cited by 19 publications

References 31 publications

Cyclic AMP prolongs graft survival by suppressing apoptosis and inflammatory gene expression in acute cardiac allograft rejection

Cyclic AMP prolongs graft survival by suppressing apoptosis and inflammatory gene expression in acute cardiac allograft rejection

A short course of mycophenolate immunosuppression inhibits rejection, but not tolerance, of rat liver allografts in association with inhibition of interleukin-4 and alloantibody responses

Revisiting liver transplant immunology: From the concept of immune engagement to the dualistic pathway paradigm

Contact Info

Product

Resources

About