The effect of thalidomide and 2 analogs on collagen induced arthritis.
OBJECTIVE
Thalidomide has been described as an inhibitor of both angiogenesis (which may account for its teratogenic effects on limb bud formation) and tumor necrosis factor-alpha (TNF-alpha) production. We evaluated its therapeutic potential in collagen induced arthritis (CIA), a rat model of rheumatoid arthritis (RA).


METHODS
Rats were administered orally 200 mg/kg/day thalidomide (n = 10) or either of 2 analogs, EM-12 (n = 9) or supidimide (n = 9). An additional group was given thalidomide (n = 10) at 200 mg/kg twice daily, and a control group (n = 13) was given vehicle only. At completion of the protocols, serum levels of TNF-alpha and vascular endothelial growth factor (VEGF) were measured.


RESULTS
Suppression of inflammatory synovitis by clinical and radiographic criteria was significantly lower in all experimental protocols except the lower dose thalidomide group. The EM-12 analog was the most efficacious, and twice daily thalidomide was better than once daily. The incidence of arthritis onset was comparable among all groups. Strong cell mediated and humoral responses to type II collagen, measured by a radiometric delayed type hypersensitivity assay and anti-type II collagen IgG ELISA, respectively, were similar in the experimental and control groups. TNF-alpha and VEGF levels were increased in all rats immunized with collagen compared to naive controls.


CONCLUSIONS
Thalidomide and its analogs can suppress the clinical severity of rat CIA, but the mechanism of action is not a result of TNF-alpha or VEGF downregulation.
Oliver
S J
SJ
Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095, USA.
Cheng
T P
TP
Banquerigo
M L
ML
Brahn
E
E
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003094:Collagen; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000097:blood / Q000494:pharmacology; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008222:Lymphokines / Q000097:blood / Q000494:pharmacology; D011859:Radiography; D051381:Rats; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D007166:Immunosuppressive Agents; D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C001079:2-(2,6-dioxopiperidin-3-yl)phthalimidine; D013792:Thalidomide; D003094:Collagen; C027948:supidimide