IL-11 protects human microvascular endothelium from alloinjury in vivo by induction of survivin expression

J Immunol. 2004 Feb 1;172(3):1391-6. doi: 10.4049/jimmunol.172.3.1391.

Abstract

IL-11 can reduce tissue injury in animal models of inflammation but the mechanism(s) is unknown. When C.B-17 SCID/beige mice bearing human skin grafts are injected i.p. with human PBMC allogeneic to the donor skin, infiltrating T cells destroy human microvessels by day 21. Intradermal injection of human IL-11 (500 ng/day) delays the time course of graft microvessel loss without reducing the extent of T cell infiltration. Protective actions of IL-11 are most pronounced on day 15. IL-11 has no effect on T cell activation marker, effector molecule, cytokine expression, or endothelial ICAM-1 expression. IL-11 up-regulates the expression of survivin, a cytoprotective protein, in graft keratinocytes and endothelial cells. Topical application of survivin antisense oligonucleotide down-regulates survivin expression in both cell types and largely abrogates the protective effect of IL-11. We conclude that in this human transplant model, IL-11 exerts a cytoprotective rather than anti-inflammatory or immunomodulatory effect mediated through induction of survivin.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Administration, Topical
  • Adult
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Cytoprotection / genetics
  • Cytoprotection / immunology*
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology*
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Injections, Intradermal
  • Interleukin-11 / administration & dosage*
  • Interleukin-11 / antagonists & inhibitors
  • Interleukin-11 / therapeutic use
  • Leukocytes, Mononuclear / transplantation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, SCID
  • Microcirculation / immunology
  • Microcirculation / metabolism
  • Microcirculation / pathology
  • Microtubule-Associated Proteins / antagonists & inhibitors
  • Microtubule-Associated Proteins / biosynthesis*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / physiology
  • Neoplasm Proteins
  • Ointments
  • Oligonucleotides, Antisense / administration & dosage
  • Skin / blood supply*
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology*
  • Skin Transplantation / adverse effects
  • Skin Transplantation / immunology
  • Skin Transplantation / pathology*
  • Survivin
  • Transplantation, Homologous / adverse effects
  • Transplantation, Homologous / immunology
  • Transplantation, Homologous / pathology

Substances

  • Adjuvants, Immunologic
  • Anti-Inflammatory Agents, Non-Steroidal
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Interleukin-11
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Ointments
  • Oligonucleotides, Antisense
  • Survivin