Pharmacological modulation by celecoxib of cachexia associated with experimental arthritis and atherosclerosis in rabbits.
OBJECTIVE
Non-steroidal anti-inflammatory drugs improve inflammatory cachexia in several conditions. Thus, we have explored inhibition of cyclooxygenase-2 (COX-2) in an experimental model of rheumatoid cachexia in rabbits.


METHODS
Chronic arthritis was induced in immunized rabbits by repeated intra-articular injections of ovalbumin. To increase the degree of systemic inflammation and also to induce atherosclerotic lesions, the animals were fed a hyperlipidaemic diet (2% cholesterol and 6% peanut oil) and were given an endothelial injury of the femoral artery. Rabbits were randomized to receive the COX-2 inhibitor celecoxib (10 mg·kg⁻¹ ·day⁻¹) or no treatment. After 4 weeks, sera, peripheral mononuclear cells and vessel specimens were collected.


RESULTS
Inhibition of COX-2 by celecoxib modulated the systemic inflammatory response and increased total cholesterol and triglyceride levels. Celecoxib also minimized weight loss and prevented serum albumin fall. At a vascular level, celecoxib reduced COX-2 protein in the femoral arterial wall, but did not modify size or the macrophage infiltration of femoral lesions nor the percentage of rabbits with spontaneous aortic plaques.


CONCLUSIONS
Our animal model induced a severe inflammatory cachexia, comparable to that of persistently active rheumatoid arthritis. The inhibition of COX-2 by celecoxib improves this state, suggesting that COX products play an important role in its development, without affecting the development or the progression of vascular lesions. Overall, these results suggest that celecoxib might be considered as a new therapeutic tool for the treatment of rheumatoid cachexia.
Romero
F I
FI
Joint and Bone Research Unit, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
Martínez-Calatrava
M J
MJ
Sánchez-Pernaute
O
O
Gualillo
O
O
Largo
R
R
Herrero-Beaumont
G
G
D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications; D001172:Arthritis, Rheumatoid / Q000150:complications*; D050197:Atherosclerosis / Q000150:complications; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology*; D011817:Rabbits; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib