A simple inflammation model that distinguishes between the actions of anti-inflammatory and anti-rheumatic drugs.
OBJECTIVE
To determine the effects of anti-inflammatory and anti-rheumatic drugs on paw swelling and changes in plasma levels of acute phase proteins (APPs) during acute inflammation in the rat.


METHODS
Inflammation was induced in rats by the injection of adjuvant and the animals were bled five days later and plasma levels of seromucoid, haptoglobin, caeruloplasmin and albumin were determined spectrophotometrically using a Cobas-bio centrifugal analyzer. The effects of daily administration of a variety of drugs used to treat arthritis were determined on paw swelling and APP levels.


RESULTS
Injection of the adjuvant induced a pronounced change in APP levels which correlated with the increase in paw swelling. In general, the NSAIDs tested significantly reduced paw swelling and significantly increased levels of haptoglobin and caeruloplasmin in a dose-related manner. Two dose-levels of steroids were administered, the higher dose reduced swelling, and reduced levels of seromucoid, haptoglobin and caeruloplasmin, but raised albumin levels; the lower dose also reduced paw swelling, but the only change in APPs was increased albumin levels. Anti-rheumatic drugs such as gold salts reduced levels of some APPs (seromucoid, haptoglobin and caeruloplasmin) without reducing paw swelling. Immunomodulators had a variety of effects on inflammation and APPs depending on mechanism of action.


CONCLUSIONS
The different classes of anti-inflammatory/anti-rheumatic drug tested show distinct profiles of activity against APPs and paw swelling. These differential effects may result from modulation of cytokine activity.
Lewis
E J
EJ
Roche Discovery Welwyn, Welwyn Garden City, Herts, UK. Jon.Lewis@roche.com
Bishop
J
J
Aspinall
S J
SJ
D000209:Acute-Phase Proteins / Q000378:metabolism; D000276:Adjuvants, Immunologic; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology; D002570:Ceruloplasmin / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006242:Haptoglobins / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D050607:Organogold Compounds; D009961:Orosomucoid / Q000378:metabolism; D011239:Prednisolone / Q000627:therapeutic use; D051381:Rats; D014221:Triamcinolone / Q000627:therapeutic use
D000209:Acute-Phase Proteins; D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D006242:Haptoglobins; D050607:Organogold Compounds; D009961:Orosomucoid; D014221:Triamcinolone; D011239:Prednisolone; D002570:Ceruloplasmin