Tacrolimus and cyclosporine differ in their capacity to overcome ongoing allograft rejection as a result of their differential abilities to inhibit interleukin-10 production1

Jiang, Hongsi; Wynn, Carmen; Fan, Ping; Ebbs, Aaron; Erickson, Laurie; Kobayashi, Masakazu

doi:10.1097/00007890-200206150-00019

Cited by 54 publications

(36 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Together these data suggest a tempo- (3,16). These data strongly point out the macrophage as the primary cell responsible for graft destruction, and rary functional deficit probably caused by loss of damaged graft tissue or due to the rapid weight gain of the support earlier observations that CsA can act directly on macrophages (8,15). growing recipients and confirms the regenerative capacity of adult porcine islets (26).…”

Section: Immunosuppression Recipient Ratssupporting

confidence: 87%

Transplantation of Long-term Cultured Porcine Islets in the Rat: Prolonged Graft Survival and Recipient Growth on Reduced Immunosuppression

et al. 2010

View full text Add to dashboard Cite

To evaluate whether further improvement in porcine islet xenotransplantation is feasible, a number of questions were addressed. Earlier we showed significant improvement in the nude mouse of the porcine islets by selection through long-term culture. Now these islets were tested in the stringent pig-to-rat model. Islets were isolated from adult pigs, cultured for 1.5-3 weeks and transplanted to rats. Possible rejection mechanisms were assessed by interference of the cellular response with cyclosporine A (CsA), blocking macrophages with gadolinium chloride (GdCl), and suppressing the humoral response with cyclophosphamide. Modifications in graft size and condition were analyzed. Untreated control recipients showed primary nonfunction (PNF). CsA treatment could fully overcome PNF and resulted in graft survival from 10 to over 134 days. Rejection was the main cause of function loss. Although rejection could not be prevented by intensifying the induction therapy, increased maintenance immunosuppression effectively blocked rejection, albeit at the expense of toxicity. Blocking the humoral response was ineffective; all grafts showed PNF. In contrast, depletion of macrophages fully prevented PNF. Combination of GdCl and CsA gave no additional effect, and grafts were rejected between 57 and 162 days. Generally, graft survivals were similar to those reported in the literature; however, long-term cultured islets required much less maintenance immunosuppression. Cessation of graft function was not always due to rejection; in some cases "islet exhaustion" was found, possibly caused by discrepancy between the graft size and the rapidly growing recipient. Neither the presence of damaged islet tissue in the graft nor the size of the graft exerted any influence on graft survival. On rejection, no real infiltration of the graft was seen; destruction gradually processed from the outside. The good functional capability of the cultured islets was illustrated by disappearance of the clinical symptoms and increase in body weight, which almost doubled in the long-term survivors.

show abstract

Section: Immunosuppression Recipient Ratssupporting

confidence: 87%

Transplantation of Long-term Cultured Porcine Islets in the Rat: Prolonged Graft Survival and Recipient Growth on Reduced Immunosuppression

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The inability of cyclosporin A to overcome ongoing allograft rejection could be addressed by cotreating recipients with neutralizing anti-IL-10 antibody. These data suggest that intragraft IL-10 production might be a critical factor in persistent rejection resulting in chronic graft injury (Jiang et al, 2002).…”

Section: Invited Review Of Il-10 Therapymentioning

confidence: 88%

Interleukin-10 Therapy—Review of a New Approach

2003

View full text Add to dashboard Cite

“…Also, there have been some studies of the influence of CSA on B cells and the humoral response (92)(93)(94). CSA did not suppress Ab production in autoimmune diseases and transplantations (95)(96)(97), suggesting that the target mechanism in T cells is different from that in B cells; CSA targets calcium activation in T cells but may not affect that pathway in B cells (93,(98)(99)(100). However, we speculate that the mechanism by which CSA enhanced Ab production here may be indirect and via induction of Treg cells.…”

Section: Discussionmentioning

confidence: 99%

“…Help for B cells might be a consequence of IL-10 production by induced Treg cells. Although IL-10 is considered to be an anti-inflammatory cytokine, its enhancement of B cell activation and Ab production has been known for decades (97,(107)(108)(109)(110). Induced Treg cells produce high levels of IL-10, and this has been suggested to lead to B cell maturation (108,111,112).…”

Section: Discussionmentioning

confidence: 99%

A Recombinant G Protein Plus Cyclosporine A–Based Respiratory Syncytial Virus Vaccine Elicits Humoral and Regulatory T Cell Responses against Infection without Vaccine-Enhanced Disease

Zhou

Zhong

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Respiratory syncytial virus (RSV) infection can cause severe disease in the lower respiratory tract of infants and older people. Vaccination with a formalin-inactivated RSV vaccine (FI-RSV) and subsequent RSV infection has led to mild to severe pneumonia with two deaths among vaccinees. The vaccine-enhanced disease (VED) was recently demonstrated to be due to an elevated level of Th2 cell responses following loss of regulatory T (Treg) cells from the lungs. To induce high levels of neutralizing Abs and minimize pathogenic T cell responses, we developed a novel strategy of immunizing animals with a recombinant RSV G protein together with cyclosporine A. This novel vaccine induced not only a higher level of neutralizing Abs against RSV infection, but, most importantly, also significantly higher levels of Treg cells that suppressed VED in the lung after RSV infection. The induced responses provided protection against RSV challenge with no sign of pneumonia or bronchitis. Treg cell production of IL-10 was one of the key factors to suppress VED. These finding indicate that G protein plus cyclosporine A could be a promising vaccine against RSV infection in children and older people.

show abstract

Tacrolimus and cyclosporine differ in their capacity to overcome ongoing allograft rejection as a result of their differential abilities to inhibit interleukin-10 production1

Abstract: Inhibition of IL-10 production is a critical factor in the ability of tacrolimus to reverse ongoing allograft rejection.

Cited by 54 publications

References 32 publications

Transplantation of Long-term Cultured Porcine Islets in the Rat: Prolonged Graft Survival and Recipient Growth on Reduced Immunosuppression

Transplantation of Long-term Cultured Porcine Islets in the Rat: Prolonged Graft Survival and Recipient Growth on Reduced Immunosuppression

Interleukin-10 Therapy—Review of a New Approach

A Recombinant G Protein Plus Cyclosporine A–Based Respiratory Syncytial Virus Vaccine Elicits Humoral and Regulatory T Cell Responses against Infection without Vaccine-Enhanced Disease

Contact Info

Product

Resources

About