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
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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) |
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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, 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: |
05 Dec 2022 15:13 |
Publisher DOI: |
10.1016/j.ejcts.2005.03.008 |
BORIS DOI: |
10.7892/boris.115412 |
URI: |
https://boris.unibe.ch/id/eprint/115412 |
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