Granulocyte colony-stimulating factor immunomodulation in the rat cardiac transplantation model

Granulocyte colony-stimulating factor (G-CSF) administration decreases tumor necrosis factor (TNF) release, an important mechanism in allograft rejection. To study G-CSF's possible antirejection effects, 30 Lewis rats underwent heart transplantation using Brown-Norway donors and were assigned varying dosages of recombinant human G-CSF (0, 20, 100, 250, and 500 mu g/kg/day) for 14 days following the operation. Recipients receiving 250 mu g/kg/day experienced an improvement in graft survival (12.3 +/- 4 days vs. 7.0 +/- 0.6 days, P<0.05, Breslow). In a separate cohort, G-CSF-treated recipients (250 mu g/kg/day x 14) killed at 2, 4, and 6 days after transplantation revealed improved serial allograft biopsy grading scores versus untreated controls (P<0.001 stratified Wilcoxon). Significant reduction in serum TNF levels was noted in the G-CSF-treated animals (P<0.025, analysis of variance). These data describe a moderate antirejection effect of G-CSF administration. Inhibition of circulating TNF in the G-CSF-treated recipients may describe a marker or a possible mechanism of this antirejection effect.