Interleukin-11 reduces T-cell-dependent experimental liver injury in mice.
Recombinant human interleukin-11 (rhIL-11) is a multifunctional cytokine that can reduce inflammation through the downregulation of multiple pro-inflammatory mediators from activated macrophages. rhIL-11 also inhibits production of several immunostimulatory cytokines such as IL-12 and interferon gamma (IFN-gamma) and has shown biological activity in multiple animal models of inflammatory disease consistent with immunomodulatory effects on macrophages and T cells. To further elucidate the anti-inflammatory activity of rhIL-11 in vivo, the effect of rhIL-11 in a model of Concanavalin A (Con-A)-induced T-cell-mediated hepatotoxicity was examined. Administration of a single dose of rhIL-11 before Con-A administration reduced centrilobular liver necrosis and enhanced survival. A dose-dependent reduction in serum levels of liver enzymes, tumor necrosis factor alpha (TNF-alpha), and IFN-gamma corresponded with this amelioration of liver damage. No significant change in infiltrating lymphocyte populations in the liver was observed following rhIL-11 treatment. Taken together, these results indicate that rhIL-11 ameliorates T-cell-mediated hepatic injury and suggests its therapeutic potential to treat inflammatory liver disease.
Bozza
M
M
Department of Molecular Medicine, Genetics Institute, Andover, MA 01810, USA.
Bliss
J L
JL
Maylor
R
R
Erickson
J
J
Donnelly
L
L
Bouchard
P
P
Dorner
A J
AJ
Trepicchio
W L
WL
D000410:Alanine Transaminase / Q000032:analysis / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D003208:Concanavalin A / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D017370:Interleukin-11 / Q000008:administration & dosage / Q000494:pharmacology*; D007376:Interleukin-2 / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D017370:Interleukin-11; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase