Viral IL-10 gene transfer decreases inflammation and cell adhesion molecule expression in a rat model of venous thrombosis.
Post-thrombotic inflammation probably contributes to chronic venous insufficiency, and little effective treatment exists. IL-10 is an anti-inflammatory cytokine that previously has been shown to decrease perithrombotic inflammation and thrombosis. We investigated in a rat model whether local expression of viral IL-10 (vIL-10) in a segment of vein that undergoes thrombosis would confer an anti-inflammatory effect and how this effect might be mediated. Rats underwent inferior vena cava isolation, cannulation, and instillation of saline or adenovirus encoding either beta-galactosidase or vIL-10. Two days after transfection, thrombosis was induced, 2 days after this the rats underwent gadolinium (Gd)-enhanced magnetic resonance venography exam, and the vein segments were harvested. Tissue transfection was confirmed by either RT-PCR of vIL-10 or positive 5-bromo-4-chloro-3-indolyl beta-d-galactopyranoside (X-Gal) staining. vIL-10 significantly decreased both leukocyte vein wall extravasation and area of Gd enhancement compared with those in controls, suggesting decreased inflammation. Immunohistochemistry demonstrated decreased endothelial border staining of P- and E-selectin, while ELISA of vein tissue homogenates revealed significantly decreased P- and E-selectin and ICAM-1 levels in the vIL-10 group compared with those in controls. Importantly, native cellular IL-10 was not significantly different between the groups. However, neither clot weight nor coagulation indexes, including tissue factor activity, tissue factor Ag, or von Willebrand factor levels, were significantly affected by local vIL-10 expression. These data suggest that local transfection of vIL-10 decreases venous thrombosis-associated inflammation and cell adhesion molecule expression, but does not directly affect local procoagulant activity.
Henke
P K
PK
Jobst Vascular Surgery Laboratory, Section of Vascular Surgery, Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
DeBrunye
L A
LA
Strieter
R M
RM
Bromberg
J S
JS
Prince
M
M
Kadell
A M
AM
Sarkar
M
M
Londy
F
F
Wakefield
T W
TW
D000818:Animals; D001780:Blood Coagulation Tests; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000378:metabolism; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000032:analysis; D018014:Gene Transfer Techniques; D004854:Herpesvirus 4, Human / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013925:Thromboplastin / Q000378:metabolism; D014162:Transfection; D014682:Vena Cava, Inferior / Q000378:metabolism / Q000473:pathology; D020246:Venous Thrombosis / Q000097:blood / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics*
C066460:BCRF1 protein, Human herpesvirus 4; D015815:Cell Adhesion Molecules; D016207:Cytokines; D014764:Viral Proteins; D016753:Interleukin-10; D013925:Thromboplastin; D011464:Epoprostenol