title: Interleukin-10 attenuates the response to vascular injury.
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.
authors.affiliation: Department of Surgery, University of Colorado Health, Sciences Center, Denver, Colorado, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Zimmerman
authors.forename: Leonid L
authors.initials: LL
authors.lastname: Reznikov
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Raeburn
authors.forename: Craig H
authors.initials: CH
authors.lastname: Selzman
mesh_terms: 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
chemical_list: D018925:Chemokines; D006133:Growth Substances; D016328:NF-kappa B; D016753:Interleukin-10