Upregulation of intragraft interleukin-10 by infusion of granulocyte colony-stimulating factor-mobilized donor leukocytes.
We examined the effects of granulocyte colony-stimulating factor (G-CSF)-mobilized donor leukocyte infusion (G-DLI) on facilitation of allograft survival using heart transplantation from DA to Lewis rats that were transiently treated with tacrolimus (2 mg/kg i.m. on day 0). Other DA rats were given G-CSF (250 microg/kg/day s.c. from days -5 to 0), and isolated leukocytes were infused into Lewis recipients after surgery. Cytokine mRNA levels were quantified by reverse transcription and real-time polymerase chain reaction. After G-CSF treatment, leukocytes in circulation increased by 7.6 times and secreted in-vitro 6.0-times-higher levels of IL-10 after lipopolysaccharide stimulation than did untreated leukocytes. G-DLI facilitated graft survival dose-dependently. Significant IL-10 mRNA upregulation was detected in grafts 24 h after surgery but not in the recipient's heart, spleen, or liver. On day 6, IFN-gamma and IL-2 mRNA levels were approximately half those of the control levels. Allograft-restricted IL-10 upregulation followed by type-1 cytokine downregulation can be achieved by the use of G-DLI.
Egi
Hiroyuki
H
Department of Surgery II, Hiroshima University Faculty of Medicine, 1-2-3 Kasumi, Minami-ku, Japan.
Hayamizu
Keisuke
K
Ohmori
Ichiro
I
Kitayama
Teruhiko
T
Asahara
Toshimasa
T
D000818:Animals; D016207:Cytokines / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016027:Heart Transplantation / Q000276:immunology*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D017708:Leukocyte Transfusion; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins; D018417:Th1 Cells / Q000276:immunology; D013997:Time Factors; D014158:Transcription, Genetic; D014184:Transplantation, Homologous
D016207:Cytokines; D011994:Recombinant Proteins; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor