Expression and significance of IL-18 in the bone marrow of patients with hematological diseases.
OBJECTIVE
To investigate the levels of IL-18 in the bone marrow of both normal subjects and patients with hematological diseases and to determine the possible significance of IL-18 in pathogenesis of some hematological malignancies.


METHODS
The IL-18 mRNA levels in the bone marrow of 140 patients with hematological diseases and 15 normal donors were determined by the semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Immunohistochemical method was used to detect IL-18 protein in 12 patients with acute myeloid leukemia (AML). The possible regulation of IL-18 for proliferation of some leukemia cells was investigated using antisense techniques.


RESULTS
IL-18 mRNA levels were obviously higher in the patients with leukemia or other malignant hematological diseases (OMHD) than in normal donors. However, no significant difference was found in the level of transcription between patients with iron deficiency anemia (IDA) and normal controls. Immunohistochemical method confirmed the presence of IL-18 protein in 10 out of 12 AML cases with positive transcription. By 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, IL-18 antisense oligodeoxynucleotides (ASON) clearly inhibited the growth of J6-1 and HL-60 cells (42% and 12% inhibited, respectively) in a dose-dependent manner.


CONCLUSIONS
IL-18 was detected at elevated levels in the bone marrow of patients with some hematological malignancies, and might be involved in the proliferation of certain leukemic cells in vivo through an autocrine mechanism.
Zhang
Bin
B
National Laboratory for Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
Rao
Qing
Q
Zheng
Guoguang
G
Cao
Zhenyu
Z
Ma
Xiaotong
X
Li
Ge
G
Lin
Yongmin
Y
Geng
Yiqi
Y
Wu
Kefu
K
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics*; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis*
D020382:Interleukin-18; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger