Differential effects of the immunosuppressants cyclosporin A, FK506 and KM2210 on cytokine gene expression.
Cyclosporin A (CsA) inhibited interleukin 2 (IL-2), IL-3, interferon gamma (IFN gamma), GM-CSF and tumor necrosis factor alpha (TNF alpha) mRNA expression in spleen cells stimulated with concavalin A (Con A) when determined by the semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. FK506 which has a similar immunosuppressive mechanism to that of CsA also showed the same inhibitory effects except for decreased IL-5 and IL-6 mRNA expression. In contrast, both CsA and FK506 enhanced transforming growth factor beta (TGF beta) and IL-1 beta mRNA expression. Another immunosuppressant KM2210 did not show any inhibitory effects on cytokine gene expression but rather enhanced IL-10, IL-6, TGF beta and IL-1 mRNA expression, thus suggesting that KM2210 has a completely different immunosuppressive mechanism from that of CsA and FK506. Anti-TFG beta 1 antibody abrogated the suppression by KM2210 of BALB/c anti-3H/He mixed lymphocyte reaction (MLR) whereas this antibody did not abrogate the suppression by CsA and FK506 of BALB/c anti-C3H/He MLR. These results indicate that TGF beta is one of the major cytokines in KM2210 immunosuppression, in addition to IL-10, but not in immunosuppression by CsA and FK506.
Han
C W
CW
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Imamura
M
M
Hashino
S
S
Zhu
X
X
Tanaka
J
J
Imai
K
K
Matsudaira
T
T
Asano
S
S
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002699:Chlorambucil / Q000031:analogs & derivatives* / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D016559:Tacrolimus / Q000494:pharmacology*
D016207:Cytokines; D017931:DNA Primers; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D002699:Chlorambucil; D004958:Estradiol; C036613:bestrabucil; D016572:Cyclosporine; D016559:Tacrolimus