Facilitation of tacrolimus-induced heart-allograft acceptability by pretransplant host treatment with granulocyte colony-stimulating factor: interleukin-12-restricted suppression of intragraft monokine mRNA expression.
BACKGROUND
Because recombinant human granulocyte colony-stimulating factor (rhG-CSF) is known to modulate function of antigen-presenting cells, we examined effects of pretransplant host treatment with rhG-CSF on allograft survival.


METHODS
In DA-to-Lewis rat heart transplantation, hosts were given pretransplant injections of rhG-CSF (250 microg/kg/day subcutaneously from day -5-0) and/or posttransplant injections of tacrolimus (2 mg/kg/day intramuscularly from day 0-3). Cytokine mRNA levels in grafts were measured by real-time reverse-transcription polymerase chain reaction.


RESULTS
rhG-CSF pretreatment was effective in prolonging allograft survival only in tacrolimus-treated hosts (P <0.001). Intragraft mRNA expression of interleukin (IL)-12 subunits (p35, p40) at 24 hours after transplantation was significantly (P <0.05) down-regulated by the addition of rhG-CSF and was associated with suppression of interferon-gamma levels on day 6, although other proinflammatory cytokines (tumor necrosis factor -alpha, IL-1beta, IL-6, IL-18) and anti-inflammatory cytokines (IL-10, transforming growth factor-beta) were not.


CONCLUSIONS
rhG-CSF pretreatment down-regulates intragraft expression of the type-1 T-helper cell (Th1)-driving cytokine IL-12 and facilitates tacrolimus-induced graft acceptance.
Kitayama
Teruhiko
T
Department of Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Hayamizu
Keisuke
K
Egi
Hiroyuki
H
Ohmori
Ichiro
I
Yoshimitsu
Masanori
M
Asahara
Toshimasa
T
D000818:Animals; D015870:Gene Expression / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016027:Heart Transplantation; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018664:Interleukin-12 / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D016559:Tacrolimus