Interleukin 10 attenuates neointimal proliferation and inflammation in aortic allografts by a heme oxygenase-dependent pathway.

Abstract

Interleukin 10 (IL-10) is a pleiotropic cytokine with well known antiinflammatory, immunosuppressive, and immunostimulatory properties. Chronic allograft rejection, characterized by vascular neointimal proliferation, is a major cause of organ transplant loss, particularly in heart and kidney transplant recipients. In a Dark Agouti to Lewis rat model of aortic transplantation, we evaluated the effects of a single intramuscular injection of a recombinant adeno-associated viral vector (serotype 1) encoding IL-10 (rAAV1-IL-10) on neointimal proliferation and inflammation. rAAV1-IL-10 treatment resulted in a significant reduction of neointimal proliferation and graft infiltration with macrophages and T and B lymphocytes. The mechanism underlying the protective effects of IL-10 in aortic allografts involved heme oxygenase 1 (HO-1) because inhibition of HO activity reversed not only neointimal proliferation but also inflammatory cell infiltration. Our results indicate that IL-10 attenuates neointimal proliferation and inflammatory infiltration and strongly imply that HO-1 is an important intermediary through which IL-10 regulates the inflammatory responses associated with chronic vascular rejection.

• Authors: Sifeng Chen, Matthias H Kapturczak, Clive Wasserfall, Olena Y Glushakova, Martha Campbell-Thompson, Jessy S Deshane, Reny Joseph, Pedro E Cruz, William W Hauswirth, Kirsten M Madsen, Byron P Croker, Kenneth I Berns, Mark A Atkinson, Terence R Flotte, C Craig Tisher, Anupam Agarwal
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 102 Issue 20 Pg. 7251-6 (May 17 2005) ISSN: 0027-8424 [Print] United States
• PMID: 15878989 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Heat-Shock Proteins
• Interleukin-10
• Oxygenases
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat

Topics

• Analysis of Variance
• Animals
• Aorta (transplantation)
• Blotting, Western
• Cell Proliferation
• Dependovirus
• Endothelial Cells (cytology)
• Enzyme-Linked Immunosorbent Assay
• Genetic Vectors
• Graft Rejection (metabolism, prevention & control)
• Heat-Shock Proteins (metabolism)
• Heme Oxygenase (Decyclizing)
• Inflammation (metabolism, prevention & control)
• Interleukin-10 (blood, genetics, metabolism)
• Oxygenases (metabolism)
• Rats
• Transgenes (genetics)
• Transplantation, Homologous