Kinetic analysis of cytokine gene expression in patients with GVHD after donor lymphocyte infusion

Patients who receive a donor lymphocyte infusion (DLI) for the treatment of relapsed leukemia after allogeneic BMT (alloBMT) often developed GVHD. To determine whether cytokines might have a role in GVHD, an intensive kinetic analysis of in vivo cytokine gene expression was performed on PBMC from three such patients. Expression of IL-1 beta, IL-2, IFN-gamma, IL-4, IL-5, IL-8, IL-10, IL-12, TNF-alpha, and IL-2R alpha was examined using a sensitive semi-quantitative reverse transcription (RT)-PCR assay system. Six normal controls were also analyzed for comparison. Expression of type 1 T helper (Th1) cytokines, IL-2 and IFN-gamma was greatly increased in all three patients. In particular, the changes in IL-2 gene expression correlated well with disease progression, suggesting that IL-2 has a critical role in the development of GVHD. Although the pattern of type 2 T helper (Th2) cytokine gene expression differed in each patient, the expression of IL-4 was inversely related to expression of Th1 cytokines, These results suggest that Th1 dominates in the development of human clinical GVHD.