Synergistic effect of low dose Cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation

Pierog, Jaroslaw; Gazdhar, Amiq; Stammberger, Uz; Gugger, Matthias; Hyde, Steven; Mathiesen, Iacob; Grodzki, Tomasz; Schmid, Ralph A. (2005). Synergistic effect of low dose Cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation. European journal of cardio-thoracic surgery, 27(6), pp. 1030-1035. Elsevier Science B.V. 10.1016/j.ejcts.2005.03.008

[img]
Preview
Text
27-6-1030.pdf - Published Version
Available under License Publisher holds Copyright.

Download (426kB) | Preview

Objective: Electroporation mediated transfer of plasmid DNA into peripheral muscle results in high transfection efficiency. The aim of this study was to investigate the effect of gene transfer of human IL-10 (hIL-10) into the tibialis anterior muscle (MTA) in combination with low dose Cyclosporine A (CsA) on acute rejection of lung allografts in the rat. Methods: Lung allotransplantation was performed from male BN donor to male Fisher F344 rats. Gene transfer was achieved by intramuscular injection into the MTA of the recipient followed by electroporation (4×20ms impulses at 200V/cm) 24h prior to the transplantation. Group A (n=5) received CsA (2.5mg/kg bw ip) for 5 days post-transplant and group B (n=5) 2.5μg of PCIK hIL-10 (plasmid expression vector containing human CMV immediate early gene promoter and enhancer) and a low dose CsA (2.5mg/kg bw i.p.). Graft function was assessed by blood gas at day 5 after exclusion of the native lung. Animals were sacrificed and blood was drawn to measure serum hIL-10 levels (ELISA) and tissue was sampled for histological grading of rejection. Results: Local expression of hIL-10 was confirmed at the mRNA level by in situ hybridization. All group A control animals showed severe signs of rejection. At day 5 all grafts in group B showed good gas exchange mean PaO2 233±123mmHg, vs 44±8mmHg in group A. Histological examination revealed moderate to severe rejection in all animals in group A (IIIB, ISHLT) in contrast to low moderate rejection in group B (II–IIIA). hIL-10 serum levels on day 5 were 14±7pg/ml in group B vs. 0 in group A. Conclusions: Electroporation mediated hIL-10 overexpression in a peripheral muscle of the recipient in combination with low dose CsA reduces acute rejection in this model of rat lung allotransplantation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Pierog, Jaroslaw Stanislaw; Stammberger, Uz Martin and Schmid, Ralph

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1010-7940

Publisher:

Elsevier Science B.V.

Language:

English

Submitter:

Marceline Brodmann

Date Deposited:

07 Oct 2020 12:10

Last Modified:

18 Mar 2021 07:50

Publisher DOI:

10.1016/j.ejcts.2005.03.008

BORIS DOI:

10.7892/boris.115412

URI:

https://boris.unibe.ch/id/eprint/115412

Actions (login required)

Edit item Edit item
Provide Feedback