Palifermin mediates immunoregulatory effects in addition to its cytoprotective effects in mice with acute graft-versus-host disease.
BACKGROUND
Treating recipient mice with palifermin (recombinant human keratinocyte growth factor) prevents the development of acute, lethal, graft-versus-host disease (GVHD). This is due, at least in part, to the ability of palifermin to protect epithelial cells from injury. Using the C57BL/6-->(C57BL/6 x DBA/2)F(1)-hybrid model, we previously showed that the protective effect of palifermin was also associated with redirection of the cytokine profile from Th1 to Th2.


CONCLUSIONS
To study this immunoregulatory effect more directly, we induced acute GVH reactions in which we treated the donors rather than the recipients with palifermin. The recipient mice were protected from GVHD-associated morbidity, and their cytokine profile was predominantly Th2. The palifermin-treated donor mice alone showed a similar Th2 cytokine profile, and we observed elevated levels of thymic stromal lymphopoietin mRNA in the thymus. We further demonstrated that treating the donor mice with palifermin protects against GVHD-associated morbidity, even if the donors are deficient in Valpha14i natural killer T cells. Our findings clearly show that palifermin mediates immunoregulatory effects in addition to its cytoprotective effects and that both are likely to be involved in the mechanism through which palifermin provides protection from acute murine GVHD.
Ellison
Cynthia A
CA
401J Brodie Center, Department of Pathology, University of Manitoba, 727 McDermot Avenue, Winnipeg, MB, Canada, R3E 3P5. ellisonc@ms.umanitoba.ca
Makar
Bryce M
BM
Wiseman
Jacqie M M
JM
Gheorghiu
Ionela
I
Taniguchi
Masaru
M
Gartner
John G
JG
D000208:Acute Disease; D000818:Animals; D002461:Cell Line, Transformed; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051523:Fibroblast Growth Factor 7 / Q000008:administration & dosage*; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D007279:Injections, Subcutaneous; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000819:agonists; D011994:Recombinant Proteins / Q000008:administration & dosage*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D016207:Cytokines; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7; D051497:Receptor, Fibroblast Growth Factor, Type 2