Effects of combinations of anti-rheumatic drugs on the production of vascular endothelial growth factor and basic fibroblast growth factor in cultured synoviocytes and patients with rheumatoid arthritis.
OBJECTIVE
To examine whether different combinations of disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX), salazosulphapyridine (SASP) and dexamethasone (DEX; a steroid), act by inhibiting the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cultured synoviocytes, causing a decrease in their serum concentrations in patients with rheumatoid arthritis (RA).


METHODS
The VEGF and bFGF concentrations in cultured synoviocytes and peripheral blood from patients with RA were measured by enzyme-linked immunosorbent assay and their serum concentrations were measured at two time points.


RESULTS
BUC and GST inhibited VEGF production even when given alone, and a combination of BUC, GST and MTX with DEX also inhibited VEGF production. None of the DMARDs or DEX inhibited bFGF production when given alone, but a combination of SASP and GST inhibited the production of bFGF in cultured synoviocytes. Serum VEGF concentrations were significantly decreased 6 months after the commencement of medication compared with their concentrations before medication.


CONCLUSIONS
Our results show that the effects of a combination of DEX with any two of BUC, GST, SASP and MTX on the production of VEGF and bFGF in cultured synoviocytes and on the serum concentrations of VEGF in patients with RA may be based on synergistic or additive effects of the drugs.
Nagashima
M
M
Department of Joint Disease and Rheumatism, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, Japan.
Wauke
K
K
Hirano
D
D
Ishigami
S
S
Aono
H
H
Takai
M
M
Sasano
M
M
Yoshino
S
S
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000097:blood; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000097:blood; D006052:Gold Sodium Thiomalate / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D008222:Lymphokines / Q000096:biosynthesis* / Q000097:blood; D008727:Methotrexate / Q000494:pharmacology*; D012460:Sulfasalazine / Q000494:pharmacology; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D016228:Endothelial Growth Factors; D008070:Lipopolysaccharides; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D006052:Gold Sodium Thiomalate; D012460:Sulfasalazine; D003907:Dexamethasone; D002097:C-Reactive Protein; D003545:Cysteine; C026535:bucillamine; D008727:Methotrexate