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Additive effects of leflunomide and tacrolimus in prevention of islet xenograft rejection

Zhang, L; Qi, Zhongquan LU ; Wu, D; Shan, S and Ekberg, Henrik LU (2004) In Scandinavian Journal of Immunology 59(3). p.255-260
Abstract
Leflunomide is a low molecular weight immunosuppressive drug which inhibits the enzymes dehydroorotate dehydrogenase and protein tyrosine kinase, both of which are important components in the immune response. As the mechanisms of action of leflunomide and tacrolimus are different, we postulated an additive or synergistic effect of the two drugs and investigated the effects of leflunomide alone, or in combination with a suboptimal dose of tacrolimus, on xenogeneic islet transplantation in a rat-to-mouse model. A total of 1200-1500 rat islets were transplanted under the left kidney capsule of streptozotocin-induced diabetic BALB/c mice. The median survival time (MST) of the untreated group was 6 days. Leflunomide at 5, 10 and 20 mg/kg/d... (More)
Leflunomide is a low molecular weight immunosuppressive drug which inhibits the enzymes dehydroorotate dehydrogenase and protein tyrosine kinase, both of which are important components in the immune response. As the mechanisms of action of leflunomide and tacrolimus are different, we postulated an additive or synergistic effect of the two drugs and investigated the effects of leflunomide alone, or in combination with a suboptimal dose of tacrolimus, on xenogeneic islet transplantation in a rat-to-mouse model. A total of 1200-1500 rat islets were transplanted under the left kidney capsule of streptozotocin-induced diabetic BALB/c mice. The median survival time (MST) of the untreated group was 6 days. Leflunomide at 5, 10 and 20 mg/kg/d administrated for 10 days significantly prolonged MST to 10, 16 and 20 days. A dose of tacrolimus (2 mg/kg/d) was associated with a graft survival of 9 (range 6-12) days; most grafts rejected during ongoing therapy. When tacrolimus (2 mg/kg/d) was combined with leflunomide (10 mg/kg/d), the survival time of the islet xenografts was increased further to 22 days, significantly longer than with leflunomide or tacrolimus alone. In summary, our findings demonstrate that leflunomide prolonged xenogeneic islet graft survival, and that its immunosuppressive effect was improved when combined with tacrolimus. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scandinavian Journal of Immunology
volume
59
issue
3
pages
255 - 260
publisher
Wiley-Blackwell
external identifiers
  • wos:000220356300003
  • pmid:15030575
  • scopus:1842452888
ISSN
1365-3083
DOI
10.1111/j.0300-9475.2004.01401.x
language
English
LU publication?
yes
id
d7b9992f-4f2a-4977-957d-a2f4c13ef1c7 (old id 284167)
date added to LUP
2007-10-26 08:53:21
date last changed
2017-01-01 07:20:51
@article{d7b9992f-4f2a-4977-957d-a2f4c13ef1c7,
  abstract     = {Leflunomide is a low molecular weight immunosuppressive drug which inhibits the enzymes dehydroorotate dehydrogenase and protein tyrosine kinase, both of which are important components in the immune response. As the mechanisms of action of leflunomide and tacrolimus are different, we postulated an additive or synergistic effect of the two drugs and investigated the effects of leflunomide alone, or in combination with a suboptimal dose of tacrolimus, on xenogeneic islet transplantation in a rat-to-mouse model. A total of 1200-1500 rat islets were transplanted under the left kidney capsule of streptozotocin-induced diabetic BALB/c mice. The median survival time (MST) of the untreated group was 6 days. Leflunomide at 5, 10 and 20 mg/kg/d administrated for 10 days significantly prolonged MST to 10, 16 and 20 days. A dose of tacrolimus (2 mg/kg/d) was associated with a graft survival of 9 (range 6-12) days; most grafts rejected during ongoing therapy. When tacrolimus (2 mg/kg/d) was combined with leflunomide (10 mg/kg/d), the survival time of the islet xenografts was increased further to 22 days, significantly longer than with leflunomide or tacrolimus alone. In summary, our findings demonstrate that leflunomide prolonged xenogeneic islet graft survival, and that its immunosuppressive effect was improved when combined with tacrolimus.},
  author       = {Zhang, L and Qi, Zhongquan and Wu, D and Shan, S and Ekberg, Henrik},
  issn         = {1365-3083},
  language     = {eng},
  number       = {3},
  pages        = {255--260},
  publisher    = {Wiley-Blackwell},
  series       = {Scandinavian Journal of Immunology},
  title        = {Additive effects of leflunomide and tacrolimus in prevention of islet xenograft rejection},
  url          = {http://dx.doi.org/10.1111/j.0300-9475.2004.01401.x},
  volume       = {59},
  year         = {2004},
}