Cellular IL-10 is more effective than viral IL-10 in decreasing venous thrombosis

Background. Systemic administration of cellular interleukin-10 (cIL-10) and gene transfection of viral interleukin-10 (vIL-10) at thrombus induction decreases vein wall inflammation. Only cIL-10, despite sharing an 84% amino acid sequence homology with vIL-10, decreases thrombosis through mechanisms yet to be determined. Methods. C57BL/6 mice (Mus musculus, n99) were studied. Inferior vena caval thrombosis was created by inferior vena caval ligation and the animals were sacrificed and evaluated at days 2 and 6 after ligation. At thrombus induction groups received intravenous 0.25 mug of cIL-10, 0.25 mug of vIL-10, or saline (untreated controls). Evaluations included thrombus mass and vein wall leukocyte counts, protein levels, and reverse-transcription polymerase chain reaction mRNA levels of P- and E-selectin, monocyte chemotactic protein-1, and IL-10. Groups were compared by analysis of variance and t tests. Results. Less thrombus was noted at both days 2 and 6 in animals treated with cIL-10. At day 2 only, vein wall leukocyte counts revealed a significant decrease in neutrophils in cIL-10 animals versus controls, with no significant differences for vIL-10 animals. In cIL-10-treated animals, P-selectin protein levels were decreased at day 6, along with a decreased thrombus mass, without significant differences in E-selectin monocyte chemotactic protein-1, or IL-10 protein levels. vIL-10 treated animals showed increased E-selectin mRNA and thrombus mass versus controls on day 6. Conclusions. cIL-10 is more antithrombotic/anti-inflammatory than vIL-10. This may be the result of cIL-10 decreasing P-selectin protein expression and vIL-10 increasing E-selectin mRNA levels. (C) 2003 Elsevier Inc. All rights reserved.