[Suppression of murine EAE by triptolide is related to downregulation of INF-gamma and upregulation of IL-10 secretion in splenic lymphocytes].
OBJECTIVE
To explore the therapeutic effectivity and the possible mechanism of triptolide (Tri) on experimental autoimmune encephalomyelitis (EAE).


METHODS
All female C57BL/6 mice were randomly divided into EAE group (28), Tri treated group (20) and adjuvant group (18). Mice in EAE and treated groups were immunized with myelin oligodendrocyte glycoprotein peptides 35-55 (MOG(35-55);), adjuvant group was injected at the same time, but instead of MOG(35-55); with normal saline. Tri was intraperitoneally injected in the dosage of 100 microg/(kg.d) in treated group on day 5 post-immunization (p.i.), and mice in EAE and adjuvant group injected with normal saline as control. The clinical feature and pathological changes were observed and the splenic lymphocytes were prepared on days 18-20 p.i. The cell cultures were divided into the control group (only 200 microL of cell suspension) and the experimental group (cell suspension in the presence of 10 mg/L MOG(35-55);). Then all of them were inoculated in 96-well flat-bottom plates under 37 degrees Celsius, 50 mL/L CO(2);. After 48 h, the proliferation assay was determined by MTT, and the supernatants were harvested for the detection of INF-gamma, IL-17, IL-10 and IL-4 by ELISA.


RESULTS
Tri treatment showed an significantly protective action on EAE. After the intervention of Tri, the levels of IL-10 were increased (P<0.05), but the secretion of INF-gamma and proliferation response of splenic lymphocytes induced by MOG(35-55); were statistically significantly inhibited(P<0.05 and P<0.01, respectively). There were no influences on the amount of IL-17 and IL-4 by Tri.


CONCLUSIONS
Tri is an effective drug in suppressing murine EAE. This suppression is supposed to be related to downregulation of INF-gamma and upregulation of IL-10 secretion in splenic lymphocytes.
Fan
Hong-cui
HC
Institute of Brain Science, Shanxi Datong University, Datong, China. fhc_002@163.com
Ren
Xiao-rong
XR
Yu
Jie-zhong
JZ
Guo
Min-fang
MF
Ji
Ning
N
Sun
Yong-sheng
YS
Liang
Li-yun
LY
Ma
Cun-gen
CG
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D010616:Phenanthrenes / Q000494:pharmacology*; D011897:Random Allocation; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017077:Culture Media, Conditioned; D004224:Diterpenes; D004852:Epoxy Compounds; D020381:Interleukin-17; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010616:Phenanthrenes; D016753:Interleukin-10; C001899:triptolide; D015847:Interleukin-4; D007371:Interferon-gamma