Combined use of etanercept and MTX restores CD4⁺/CD8⁺ ratio and Tregs in spleen and thymus in collagen-induced arthritis.
OBJECTIVE
To further explore the mechanism of etanercept (ENT, rhTNFR:Fc) and methotrexate (MTX) in the combined treatment of rheumatoid arthritis (RA), we investigated whether thymic and splenic T-cell subsets and their related cytokines imbalance could be restored by ETN/MTX treatment.


METHODS
The effect of ETN/MTX on collagen-induced arthritis (CIA) was evaluated by arthritis scores, joint and spleen histopathology, as well as indices of thymus and spleen. T lymphocytes proliferation was determined by [(3)H]-TdR incorporation. Levels of TNF-α, LT-α, IL-1β, RANKL, IL-10, IL-17, IFN-γ and IL-6 were detected by enzyme linked immunosorbent assay. The subsets of T lymphocytes including CD4(+), CD8(+), CD3(+)CD4(+), CD4(+)CD25(+), CD4(+)CD62L(+) and CD4(+)CD25(+)Foxp3(+) cells were quantified using flow cytometry.


RESULTS
Combined administration of ETN/MTX significantly inhibited the proliferation of T lymphocytes, decreased serum IL-6, TNF-α, IL-1β, RANKL and macrophage supernatant IL-17, LT-α, increased serum IFN-γ and macrophage supernatant IL-10. Moreover, the combined administration could restore CD4(+)/CD8(+) ratio and Treg cells of CIA thymus and spleen.


CONCLUSIONS
Taken together, our findings suggest that ENT/MTX may modify the abnormal T lymphocytes balance from central to peripheral lymphoid organs, which may partially, explained the mechanism of the combined administration.
Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry, Institute of Clinical Pharmacology, Anhui Medical University, 81, Meishan Road, Hefei, 230032 Anhui, People's Republic of China. hzhb1987@126.com
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B
Huang
Q T
QT
Wang
S S
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Song
Y J
YJ
Wu
Y K
YK
Ma
L L
LL
Zhang
J Y
JY
Chen
H X
HX
Wu
L
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Jiang
W
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Wei
D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001169:Arthritis, Experimental / Q000097:blood / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology* / Q000473:pathology; D016516:CD4-CD8 Ratio; D016207:Cytokines / Q000097:blood; D000068800:Etanercept; D007074:Immunoglobulin G / Q000008:administration & dosage*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D051379:Mice; D008811:Mice, Inbred DBA; D053245:RANK Ligand / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology
D018501:Antirheumatic Agents; D016207:Cytokines; D007074:Immunoglobulin G; D053245:RANK Ligand; D018124:Receptors, Tumor Necrosis Factor; C505689:Tnfsf11 protein, mouse; D000068800:Etanercept; D008727:Methotrexate