Decrease in cellularity and expression of adhesion molecules by anti-tumor necrosis factor alpha monoclonal antibody treatment in patients with rheumatoid arthritis.
OBJECTIVE
The effect of chimeric anti-tumor necrosis factor alpha (TNF alpha) monoclonal antibody (MAb) therapy on synovial inflammation was studied in order to address the hypothesis that anti-TNF alpha therapy leads to down-regulation of adhesion molecules and a decrease in inflammatory cell influx in synovial tissue (ST).


METHODS
The immunohistologic features of synovial biopsy specimens, both before and 4 weeks after anti-TNF alpha MAb (cA2) therapy, were studied in 14 patients with rheumatoid arthritis (RA). The patients either received a placebo (n = 2), or were given intravenous doses of cA2 at 10 mg/kg (n = 5) or 20 mg/kg (n = 7).


RESULTS
A significant (P < 0.03) reduction in the mean scores for T cells and for the adhesion molecules, vascular cell adhesion molecule 1 and E-selectin, was observed after therapy with 10 mg/kg or 20 mg/kg of cA2 in RA patients.


CONCLUSIONS
The reduced expression of adhesion molecules, and the decrease in cellularity of rheumatoid ST after cA2 administration support the hypothesis that the antiinflammatory effect of anti-TNF alpha therapy might be partly explained by down-regulation of cytokine-inducible vascular adhesion molecules in ST, with a consequent reduction of cell traffic into joints.
Tak
P P
PP
Leiden University Hospital, The Netherlands.
Taylor
P C
PC
Breedveld
F C
FC
Smeets
T J
TJ
Daha
M R
MR
Kluin
P M
PM
Meinders
A E
AE
Maini
R N
RN
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D004311:Double-Blind Method; D019040:E-Selectin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1