Liposome-mediated intraperitoneal interleukin 10 gene transfer increases survival in cecal litigation and puncture model of sepsis.
Interleukin 10 (IL-10) has been considered to alleviate the inflammatory cytokine response in various models of sepsis. Although being regarded as a key immunomodulator molecule to be beneficial for the treatment of sepsis, recombinant IL-10 treatment is limited by efficacy and tolerability. We tested a novel approach and conducted i.p. liposomal IL-10 gene transfer 24 h before the cecal ligation and puncture in mice and observed 75% mortality at the end of the 7th day. The mortality was 100% in the group where the gene transfer was not performed. The transgene expression is observed mainly in the endothelium in all vital organs. The results demonstrate the advantageous role of de novo IL-10 synthesis in early stages of sepsis and suggest the beneficial impact of gene transfer approach to recombinant protein infusions.
Kabay
Burhan
B
Hacettepe University, Faculty of Medicine, Department of General Surgery, Ankara, Turkey.
Kocaefe
Y Cetin
YC
Baykal
Atac
A
Ozguc
Meral
M
Sayek
Iskender
I
D000818:Animals; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D016753:Interleukin-10 / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage; D018805:Sepsis / Q000628:therapy*
C508609:IL10 protein, human; D008081:Liposomes; D011994:Recombinant Proteins; D016753:Interleukin-10