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-1beta, IL-2, IFN-gamma, IL-4, IL-5, IL-8, IL-10, IL-12, TNF-alpha, and IL-2Ralpha 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.
Das
H
H
Hyogo Institute of Clinical Research, Hyogo, Japan.
Imoto
S
S
Murayama
T
T
Mizuno
I
I
Sugimoto
T
T
Taniguchi
R
R
Toda
K
K
Isobe
T
T
Nakagawa
T
T
Nishimura
R
R
Koizumi
T
T
D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007378:Interleukins / Q000235:genetics; D007700:Kinetics; D007938:Leukemia / Q000628:therapy; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008137:Longitudinal Studies; D017710:Lymphocyte Transfusion / Q000009:adverse effects*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma