Baris YILDIZ, Parisa SHARAFİ, TAMER ÇIRAK, BARLAS SULU, Çetin KOCAEFE, MEHMET BÜLENT TIRNAKSIZ

Comparison of intravenous versus intraperitoneal interleukin-10 gene delivery in mouse model of sepsis

Sepsiste IL-10 kullanımına yönelik en yaratıcı yöntem IL-10un deneysel modelde gen tedavisi şeklinde verilmesidir. Biz çalışmamızda IL-10un erken sepsiste intravenöz ve intraperitoneal kinetiğini karşılaştırdık. Araştırmamız prospektif kontrollü çalışmadır. Yirmi adet Swiss-Albino dişi fare kullanılarak altı grup oluşturulmuştur. İntra-abdominal sepsis çekal ligasyon ve ponksiyon (ÇLP) yöntemiyle ortaya çıkarılmıştır. Deney hayvanlarına ya intraperitoneal veya intravenöz olarak IL-10 lipozomal gen transferi yapılmıştır. Hayvanlar enjeksiyon sonrası 24. saatte sakrifiye edilmişlerdir. Bunu akciğer, karaciğer, dalak, vena kava dokularının çıkarılması izlemiştir. İmmünhistokimyasal boyamada intraperitoneal verilişten sonra karaciğer boyanmasının daha belirgin olduğu görülmüştür. İntravenöz verilişten sonra tüm endotelyal dokuların boyandığı görülmüştür. Transgenin doku ekspresyonunun ÇLP ve intravenöz enjeksiyon yapılan grupta diğer gruplara göre çok daha belirgin olduğu görülmüştür. Sonuçlarımız aynı zamanda göstermiştir ki IL-10un pro-inflamatuar etkisi intravenöz verilişte daha belirgindir ve kendisini IL-6 indüksiyonuyla göstermektedir. IL-10 un halen keşfedilmeyi bekleyen tedavi edici özelliği vardır.

Farelerde intraabdominal sepsis modelinde intravenöz ve intraperitoneal interlökin 10 lipozom aracılı gen tedavisinin karşılaştırılması

The most novel approach utilizing IL-10 in sepsis is IL-10 gene delivery in experimental model of sepsis. In our study, we aimed to compare kinetics of intravenous versus intraperitoneal delivery of IL-10 gene transfer in early stages of sepsis. This is a prospective controlled experimental study. Six groups were gathered with 20 Swiss-Albino female mice. Intra-abdominal sepsis was induced by cecal ligation and puncture (CLP). Animals had either intraperitoneal or intravenous IL-10 liposomal gene transfer. Animals were sacrified 24 h after injections, followed by harvest of lung,liver,spleen,vena cava tissues. Immunostaining revealed more prominent staining in liver after intraperitoneal delivery. All endothelial tissues stained with intravenous delivery. There was striking difference between tissue expressions of transgene of animals in CLP intravenous group when compared to other groups. Our results point out that pro-inflammatory action of IL-10 is prominent in intravenous gene delivery which shows itself with induction of zyon. IL-10 still may harbor therapeutical potential which still needs to be explored.

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