Upregulation of intragraft interleukin-10 by infusion of granulocyte colony-stimulating factor-mobilized donor leukocytes

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Abstract
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 μ/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‐γ 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.