Downregulation of both interleukin-12 and interleukin-2 in heart allografts by pretransplant host treatment with granulocyte colony-stimulating factor and tacrolimus.
Since recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been reported to induce immune deviation, we examined the effects of pretransplant treatment of recipients with rhG-CSF on heart allograft survival. Before heterotopic heart transplantation from DA to Lewis rats, recipients were given rhG-CSF (125microg/kg s.c. twice a day from day -5 to 0) and/or tacrolimus (2mg/kg i.m. on day 0). Combined treatment with both rhG-CSF and tacrolimus prolonged graft survival significantly (P<0.05), while rhG-CSF or tacrolimus alone did not. At 24h after transplantation, cytokine mRNA levels in the grafts were measured by reverse transcription and real-time polymerase chain reaction. IL-12 p35 expression was highly inhibited by rhG-CSF treatment, but tacrolimus did not change the levels. Conversely, rhG-CSF treatment did not affect IL-2 levels, while tacrolimus completely blocked its expression. Combined pretreatment was effective for suppressing acute rejection reaction by downregulating these two key type-1 cytokines, IL-12 and IL-2, with unchanged levels of IL-10.
Department of Surgery II, Hiroshima University Faculty of Medicine, Hiroshima, Japan.
Hiroyuki
H
Egi
Keisuke
K
Hayamizu
Teruhiko
T
Kitayama
Ichiro
I
Ohmori
Masazumi
M
Okajima
Toshimasa
T
Asahara
D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D053765:Interleukin-12 Subunit p35; D007376:Interleukin-2 / Q000235:genetics*; D008297:Male; D021122:Protein Subunits / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous
C508858:IL12A protein, human; D053765:Interleukin-12 Subunit p35; D007376:Interleukin-2; D021122:Protein Subunits; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D016559:Tacrolimus