IL-10 regulates thrombus-induced vein wall inflammation and thrombosis.
Vein wall inflammation associated with venous thrombosis is mediated by an imbalance in proinflammatory as compared with antiinflammatory molecules. We hypothesize that IL-10 is an important antiinflammatory cytokine that influences vein wall inflammation and thrombus propagation during venous thrombosis. To test this hypothesis a model of inferior vena caval thrombosis was used. Studies were performed at sacrifice 2 days after thrombus induction and included leukocyte morphometrics, myeloperoxidase activity, vein wall permeability, thrombus weight, and IL-10 ELISA analysis from the vein wall. IL-10 was elevated in the vein wall during venous thrombosis. Neutralization of IL-10 increased inflammation, while supplementation with rIL-10 demonstrated a dose- and time-dependent decrease in inflammation. Interestingly, a low 2.5-microg rIL-10 dose given at time of initiation of thrombosis most significantly decreased inflammation. Thrombus weight was importantly diminished by reconstitution of IL-10. These studies support an important role for IL-10 in the regulation of thrombus-associated inflammation and thrombosis and suggest that IL-10 could be used as a therapeutic agent in the treatment of venous thrombosis.
Downing
L J
LJ
Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109, USA.
Strieter
R M
RM
Kadell
A M
AM
Wilke
C A
CA
Austin
J C
JC
Hare
B D
BD
Burdick
M D
MD
Greenfield
L J
LJ
Wakefield
T W
TW
D000818:Animals; D003251:Constriction, Pathologic; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D007106:Immune Sera / Q000008:administration & dosage; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D007275:Injections, Intravenous; D016753:Interleukin-10 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D013924:Thrombophlebitis / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D013927:Thrombosis / Q000276:immunology; D014682:Vena Cava, Inferior / Q000473:pathology
D007106:Immune Sera; D011994:Recombinant Proteins; D016753:Interleukin-10