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Interleukin-10 attenuates the response to vascular injury. J Surg Res 2004 Oct;121(2):206-13

Date

10/27/2004

Pubmed ID

15501460

DOI

10.1016/j.jss.2004.03.025

Scopus ID

2-s2.0-6344258590   35 Citations

Abstract

BACKGROUND: The inflammatory response to vascular injury is characterized by expression of cytokines, growth factors, and chemokines that conspire to promote vessel remodeling and intimal hyperplasia (IH). Interleukin-10 (IL-10) is a multifunctional cytokine that has several anti-inflammatory properties in vitro. Few studies have evaluated the effects of IL-10 in experimental atherosclerosis. The purpose of the present study was to determine the influence of IL-10 on vascular inflammation and IH following mechanical injury.

METHODS: Wire carotid injury was performed in wild-type (WT) mice with and without IL-10 treatment. Immunohistochemistry, PCR, and ELISA assays were used to examine vessel production of basic fibroblast growth factor (bFGF), monocyte chemotactic protein-1 (MCP-1), and nuclear factor kappa B (NFkappaB). Vessels were morphometrically analyzed for IH.

RESULTS: Carotid injury induced early expression of MCP-1 and bFGF that was abrogated in mice treated with IL-10. Similarly, injury-induced expression of NFkappaB message and protein was attenuated in mice receiving exogenous IL-10. Compared to untreated mice, IL-10 markedly decreased levels of IH. Interestingly, carotid injury in IL-10-deficient mice resulted in an augmented IH response compared to injured WT mice.

CONCLUSIONS: In an in vivo model of direct vascular injury, IL-10 decreased expression of the pro-inflammatory transcription factor, NFkappaB, and the mitogenic chemokine and growth factor, MCP-1 and bFGF, respectively. These observations were associated with IL-10-induced attenuation of IH. Furthermore, endogenous IL-10 appeared to suppress the injury response. In conclusion, exogenously delivered IL-10 may represent a clinically relevant anti-inflammatory strategy for post-injury intimal hyperplasia.

Author List

Zimmerman MA, Reznikov LL, Raeburn CD, Selzman CH

Author

Michael A. Zimmerman MD, FACS Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Carotid Arteries
Carotid Artery Injuries
Chemokines
Growth Substances
Hyperplasia
Immunohistochemistry
Interleukin-10
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-kappa B
Reverse Transcriptase Polymerase Chain Reaction
Tunica Intima
Vasculitis
Wounds, Nonpenetrating
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0