Intercellular adhesion molecule-1 expression in adjuvant arthritis in rats: inhibition by kappa-opioid agonist but not by NSAID.
OBJECTIVE
To quantify intercellular adhesion molecule-1 (ICAM-1) expression in normal and adjuvant arthritic rats and to determine the extent to which ICAM-1 expression in arthritic animals is altered by treatment with a prototype nonsteroidal antiinflammatory drug (NSAID) and a kappa-opioid agonist.


METHODS
Unilateral hind paw inflammation was induced by intradermal injection of Freund's complete adjuvant (FCA) into the right hind paw of female Lewis rats. Polyarthritis was induced by intradermal injection of FCA into the base of the tail of female dark Agouti rats. The NSAID naproxen [5 mg/kg intraperitoneally (ip)] or the kappa-opioid PD117302 (15 mg/kg ip) was administered twice daily throughout the experiment (21 days). ICAM-1 expression was quantified using monoclonal antibodies against rat ICAM-1 that bind to the endothelium in proportion to the degree of adhesion molecule expression.


RESULTS
ICAM-1 expression was significantly upregulated in the joints of affected limbs of animals with both unilateral hind paw inflammation and polyarthritis. In animals treated with PD 117302 and naproxen there was a significant attenuation of arthritis; however, only treatment with PD117302 was able to significantly inhibit the upregulation of ICAM-1 expression in arthritic joints.


CONCLUSIONS
ICAM-1 expression is upregulated in experimental arthritis. It appears that the kappa-opioid PD117302, but not the NSAID naproxen, inhibits the upregulation of ICAM-1 in arthritic joints, suggesting these agents act via different mechanisms. The ability of the kappa-agonist, PD117302, to inhibit both the inflammation and upregulation of ICAM-1 in arthritic joints emphasizes the potential of kappa-agonists as antiarthritic agents.
Wilson
J L
JL
School of Physiology and Pharmacology, University of New South Wales, Sydney, Australia.
Walker
J S
JS
Antoon
J S
JS
Perry
M A
MA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000235:genetics*; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000235:genetics; D009288:Naproxen / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013876:Thiophenes / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009294:Narcotics; D011758:Pyrroles; D017473:Receptors, Opioid, kappa; D013876:Thiophenes; C054718:PD 117302; D018799:Intercellular Adhesion Molecule-1; D009288:Naproxen