Effects of 15-deoxyspergualin in vitro and in vivo on cytokine gene expression.
Reverse transcriptase-polymerase chain reaction showed that interleukin 3, IL-4, IL-5, IL-6, interferon-gamma and stem cell factor mRNA expression were higher in 15-deoxyspergualin-treated spleen cells than in control spleen cells. Increased IL-2 and IFN-gamma mRNA expression were observed in 15-deoxyspergualin-treated bone marrow cells. On the other hand, increased platelet counts in BALB/c-->C3H/He bone marrow chimeras were observed from days 20 to 33 in our previous work, when they were treated with 15-deoxyspergualin from days 14 to 25. In contrast, marked leukocytopenia and anemia were simultaneously observed, although a marked leukocytosis and a rapid recovery of anemia were observed on day 33 and thereafter. To analyze effects of 15-deoxyspergualin on hematopoiesis and the immune system, we examined mRNA expression in bone marrow and spleen cells from BALB/c-->C3H/He bone marrow chimeras treated with 15-deoxyspergualin from days 14 to 25. Reverse transcriptase-polymerase chain reaction showed that IL-3, IL-4, IL-6, stem cell factor, granulocyte colony-stimulating factor, and granulocyte/macrophage colony-stimulating factor mRNA expression were higher in 15-deoxyspergualin-treated chimeras than in control chimeras, indicating that these cytokines are responsible for an enhancement of hematopoiesis. It was conceivable that IL-6 supported thrombopoiesis in concert with other cytokines. On the contrary, increased IFN-gamma, IL-2, IL-3, IL-4, and IL-10 mRNA expression may play an immunosuppressive role in vivo.
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
X
X
Zhu
M
M
Imamura
J
J
Tanaka
C W
CW
Han
S
S
Hashino
K
K
Imai
M
M
Asano
A
A
Nakane
T
T
Minagawa
M
M
Kobayashi
D000199:Actins / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells; D002678:Chimera; D016207:Cytokines / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000199:Actins; D016207:Cytokines; D006146:Guanidines; D007376:Interleukin-2; D015848:Interleukin-5; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; C037258:gusperimus