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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / administration & dosage
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Administration, Topical
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Adult
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
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Cytoprotection / genetics
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Cytoprotection / immunology*
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Down-Regulation / genetics
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Down-Regulation / immunology
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Endothelium, Vascular / immunology
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Endothelium, Vascular / metabolism*
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Endothelium, Vascular / pathology*
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Humans
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Inhibitor of Apoptosis Proteins
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Injections, Intradermal
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Interleukin-11 / administration & dosage*
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Interleukin-11 / antagonists & inhibitors
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Interleukin-11 / therapeutic use
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Leukocytes, Mononuclear / transplantation
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, SCID
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Microcirculation / immunology
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Microcirculation / metabolism
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Microcirculation / pathology
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Microtubule-Associated Proteins / antagonists & inhibitors
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Microtubule-Associated Proteins / biosynthesis*
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / physiology
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Neoplasm Proteins
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Ointments
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Oligonucleotides, Antisense / administration & dosage
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Skin / blood supply*
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Skin / immunology
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Skin / metabolism
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Skin / pathology*
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Skin Transplantation / adverse effects
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Skin Transplantation / immunology
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Skin Transplantation / pathology*
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Survivin
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Transplantation, Homologous / adverse effects
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Transplantation, Homologous / immunology
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Transplantation, Homologous / pathology
Substances
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Adjuvants, Immunologic
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Anti-Inflammatory Agents, Non-Steroidal
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BIRC5 protein, human
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Inhibitor of Apoptosis Proteins
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Interleukin-11
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Microtubule-Associated Proteins
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Neoplasm Proteins
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Ointments
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Oligonucleotides, Antisense
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Survivin