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.