Development of a rapid screen for detecting and differentiating immunomodulatory vs. anti-inflammatory compounds in rats.
Polyarthritis can be induced in rats using a synthetic adjuvant, N,N-dioctyldecyl-N', N-bis(2-hydroxyethyl) propanediamine (LA) suspended in oil. The disease is morphologically indistinguishable from the classic adjuvant arthritis induced by Freund's complete adjuvant (FCA). LA injection (7.5 mg/animal) consistently induced paw swelling, splenomegaly and fibrinogen level increases at certain time points. Studies evaluating various protocols and parameters determined that a 15 day assay where agents administered from days 9 through 13, would differentiate immunomodulatory and anti-inflammatory compounds. Parameters utilized were body weight, paw volumes, spleen weights, and fibrinogen levels. Immunomodulatory agents reduce paw swelling, splenomegaly and in some cases fibrinogen levels. NSAIDS reduce paw swelling, increase splenomegaly and have no effect on fibrinogen levels. These results indicate that compounds active in the traditional FCA assay can be detected and differentiated with respect to anti-inflammatory vs. immunomodulatory activity in a rapid screen.
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Eli Lilly and Company, Indianapolis, IN 46285.
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D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000473:pathology; D003959:Diamines; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005340:Fibrinogen / Q000378:metabolism; D005528:Foot / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D013154:Spleen / Q000473:pathology
D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003959:Diamines; D005340:Fibrinogen; C006270:avridine