Histological analysis of synovium by treatment of etanercept for rheumatoid arthritis.
OBJECTIVE
In order to investigate the histological change in effect attenuation cases of etanercept compared with methotrexate (MTX), we performed immunohistochemical examination by seven different molecules.


METHODS
We histologically assessed synovial tissue from five MTX-treated rheumatoid arthritis (RA) patients as control and six etanercept and MTX-treated RA patients after synovectomy by arthroscopy. The synovium of both groups were assessed by hematoxylin and eosin (HE) and we also analysed the expression of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), B-cell precursors and mature B-cell transmembrane protein, CD20, macrophage marker, CD68, bromodeoxyuridine (BrdU) and vascular endothelial growth factor (VEGF) by immunohistochemistry.


RESULTS
HE staining showed vascular and cell proliferations of the synovium of the RA patients who received etanercept compared with the control MTX group. TNF-alpha and IL-6 were expressed in both groups.MMP-3 and CD68 expressed less significantly in the etanercept group compared with the control (P < 0.05). CD20 strongly expressed in the etanercept group significantly (P < 0.05). BrdU expressed in the synovium in the etanercept group significantly (P < 0.05). VEGF was not found overall in both group.


CONCLUSIONS
Based on the histological change of synovium, treatment by etanercept may be involved in vascular and cell proliferations with inhibition of the expression of CD68 and MMP-3 in synovium of RA patients. These findings indicate immunohistochemical change of synovium with etanercept is one of the mechanism of efficacy of etanercept.
Suzuki
Yutaka
Y
Department of Orthopaedic Surgery, Tokyo Women's Medical University, Medical Center East, 2-1-10 Nishiogu, Arakawa, Tokyo 116-8567, Japan.
Inoue
Kazuhiko
K
Chiba
Junji
J
Inoue
Yasuo
Y
Kanbe
Katsuaki
K
D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D000068800:Etanercept; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018501:Antirheumatic Agents; D015415:Biomarkers; D000068800:Etanercept; D007074:Immunoglobulin G; D015850:Interleukin-6; D019278:Matrix Metalloproteinase 3; D008727:Methotrexate; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C508600:IL6 protein, human