Anti-inflammatory and immuno-modulatory effects of novel retinoid-like 2,4,6,8-nonatetraenoic acids (NTA) in adjuvant-induced arthritis.
Prophylactic treatment (p.o.) of rats with adjuvant-induced arthritis (AA) with two retinoid-like 2,4,6,8-nonatetraenoic acids (NTA), Ro 23-6457 and Ro 23-2895, significantly reduced hind paw swelling between days 10-23 and the level of plasma fibrinogen (MED approximately 25 mumoles/kg). When given therapeutically (75 mumoles/kg between day 21 and 28) either NTA arrested the progression of the disease (MED, 25-75 mumoles/kg). Unseparated and adherent cell (AC) depleted spleen cells from rats with AA (day 12-15) responded poorly to the T cell mitogen, Con A (2.5 micrograms/ml) and the B cell mitogen, LPS (10 micrograms/ml). The responses were partially restored (approximately 30% of normal responses) in AC-depleted (but not unseparated) spleen cells from Ro 23-6457 treated rats (75 and 250 mumoles/kg/day). These data demonstrate an immunomodulatory effect of Ro 23-6457 in the adjuvant rat which may contribute to its anti-inflammatory activity in AA.
Hanglow
A C
AC
Department of Pharmacology and Chemotherapy, Hoffmann-La Roche Inc., Nutley, NY 07110.
Rosenberger
M
M
Lovey
A J
AJ
Nemzek
R
R
Welton
A F
AF
Coffey
J W
JW
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001168:Arthritis; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy*; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005340:Fibrinogen / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008934:Mitogens; D051381:Rats; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D008934:Mitogens; C061341:Ro 23-2895; C061340:Ro 23-6457; D014212:Tretinoin; D005340:Fibrinogen