Proteins of rat serum V: adjuvant arthritis and its modulation by nonsteroidal anti-inflammatory drugs.
The effect of adjuvant arthritis (AA) on the pattern of rat serum proteins includes the upregulation of haptoglobin, orosomucoid, alpha2-macroglobulin, serine protease inhibitor-3, thiostatin, alpha1-antitrypsin, C-reactive protein, and the downregulation of kallikrein-binding protein, alpha1-inhibitor III, apolipoprotein A-I, alpha2-HS-glycoprotein, albumin, apolipoprotein A-IV, transthyretin and transferrin. Minor changes (+/- 20%) are observed for Gc-globulin, ceruloplasmin, and alpha1-macroglobulin. AA thus grossly resembles the acute inflammatory response elicited by the injection of turpentine, although the changes in the levels of negative acute-phase proteins (APP) are smaller in acute inflammation. Indomethacine and ibuprofen inhibit the effects of arthritis on the synthesis of rat serum proteins in different ways: The former is, on average, three times as effective as the latter. Each drug interferes differently with different proteins. In animals without AA, both nonsteroidal anti-inflammatory drugs (NSAID) mimic the inflammatory pattern to a certain extent, with more effect on the negative than on the positive APPs. Overall, the shifts in serum protein levels parallel changes in inflammatory parameters such as joint swelling and serum interleukin-6 (IL-6) activity. Protein quantitation after two-dimensional electrophoresis (2-DE) reveals some effects of the drugs per se which escape detection by other routine tests.
Ebrini
I
I
Istituto di Ricerche Farmacologiche Mario Negri, Università degli Studi, Milano, Italy.
Agnello
D
D
Miller
I
I
Villa
P
P
Fratelli
M
M
Ghezzi
P
P
Gemeiner
M
M
Chan
J
J
Aebersold
R
R
Gianazza
E
E
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy*; D001798:Blood Proteins / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D007213:Indomethacin / Q000009:adverse effects / Q000627:therapeutic use*; D013058:Mass Spectrometry; D051381:Rats; D011917:Rats, Inbred Lew
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D007213:Indomethacin