Interleukin-10 attenuates the response to vascular injury.
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.
Zimmerman
Michael A
MA
Department of Surgery, University of Colorado Health, Sciences Center, Denver, Colorado, USA.
Reznikov
Leonid L
LL
Raeburn
Christopher D
CD
Selzman
Craig H
CH
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020212:Carotid Artery Injuries / Q000150:complications* / Q000473:pathology*; D018925:Chemokines / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006965:Hyperplasia; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*; D014657:Vasculitis / Q000209:etiology*; D014949:Wounds, Nonpenetrating / Q000150:complications / Q000473:pathology
D018925:Chemokines; D006133:Growth Substances; D016328:NF-kappa B; D016753:Interleukin-10