Efficacy of interleukin 10 gene hydrofection in pig liver vascular isolated ‘in vivo’ by surgical procedure with interest in liver transplantation

English version

Autoři: Luis Sendra ^aff001; María José Herrero ^aff001; Eva María Montalvá ^aff003; Inmaculada Noguera ^aff005; Francisco Orbis ^aff004; Ana Díaz ^aff005; Rafael Fernández-Delgado ^aff006; Rafael López-Andújar ^aff003; Salvador F. Aliño ^aff001
Působiště autorů: Pharmacogenetics Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain ^aff001; Gene Therapy Unit, Department of Pharmacology, Universitat de Valencia, Valencia, Spain ^aff002; Unit of Experimental Hepatology and Liver Transplantation, Instituto de Investigación Sanitaria La Fe, Valencia, Spain ^aff003; HPB Surgery and Transplant Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain ^aff004; SCSIE, Central Services of Experimental Support, Universitat de Valencia, Valencia, Spain ^aff005; Pediatrics Unit, Department of Pediatrics, Obstetrics and Gynecology, Universitat de Valencia, Valencia, Spain ^aff006; Clinical Pharmacology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain ^aff007
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0224568

Souhrn

Aim

Liver transplantation is the only curative strategy for final stage liver diseases. Despite the great advances achieved during the last 20 years, the recipient immune response after transplantation is not entirely controlled. This results in high rates of acute cell rejection and, approximately, 10% of early mortality. Therapeutic treatment could be improved by efficiently transfecting genes that encode natural immunosuppressant proteins, employing safe procedures that could be transferred to clinical setting. In this sense, interleukin 10 plays a central role in immune tolerance response by acting at different levels.

Methods

hIL10 gene was hydrofected by retrograde hydrodynamic injection in pig liver with complete vascular exclusion mediated by an ‘in vivo’ surgical procedure. Levels of IL10 DNA, RNA and protein were determined within liver tissue 1 and 10 days after the injection and, more frequently, also the interleukin-10 protein in peripheral blood.

Results

The procedure was safe for the animals and neither hemodynamic parameters nor liver function determinations showed relevant alterations. The hIL10 hydrofection in watertight liver mediated efficient gene transfer and this was transcribed and translated to protein, achieving up to 110 pg/ml of IL10 in peripheral blood. This value is close to that considered able to reduce the activity of TNFα by half (IL10 IC₅₀ for TNFα = 124 pg/ml).

Conclusions

Results of this work suggest that IL10 liver hydrofection with vascular exclusion in vivo is a safe and transferable procedure that mediates plasma protein levels with potential clinical interest in immune modulation after transplantation.

Klíčová slova:

Cytokines – Surgical and invasive medical procedures – Liver transplantation – Liver – Vascular surgery – Swine – Gene delivery – Gene transfer

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