The immunomodulatory effects of
Wy-41,770 (5H-dibenzo[a,d]cyclohepten-5-ylidene)
acetic acid, were compared to
levamisole and
indomethacin in several in vivo models. In the Jerne plaque assay,
Wy-41,770 (1 and 100 mg/kg, p.o.) administered on day 1 after sensitization suppressed
IgM plaque forming cells (PFC) while
levamisole was active when given on days 1 and 2 after sensitization. In contrast,
indomethacin administered on days 2 and 3 after sensitization increased PFC. In the rat
experimental allergic encephalomyelitis (EAE) model,
Wy-41,770 reduced limb
paralysis at 10 and 100 mg/kg, p.o. when dosed before sensitization.
Indomethacin was active too when predosed in the rat EAE model. In the
methylated bovine serum albumin model (
MBSA)
delayed hypersensitivity (DH) model in mouse,
Wy-41,770 (10 mg/kg, p.o.) given on day 1 prior to sensitization and day 2 after sensitization in subliminally sensitized animals augmented the DH response while inhibiting the subliminal DH response when administered at 6 hr after challenge.
Levamisole showed similar activity in this subliminal model while
indomethacin given 6 hr post challenge was inhibitory. All three drugs were inactive in mice normally sensitized to
MBSA at the same
drug regimens. In guinea pigs, subliminally sensitized to
tuberculin,
Wy-41,770 (10 and 100 mg/kg, p.o.) and
levamisole augmented the DH response. No changes in DH response were observed for both drugs in normally sensitized guinea pigs. In the rat adjuvant arthritic model,
Wy-41,770 (5 and 15 mg/kg, p.o.) inhibited day 16 uninjected paw
edema and restored significantly the depressed proliferative responses to
mitogen by spleen cells taken from the same arthritic rats at day 16. The moderate immunomodulatory activity of
Wy-41,770 may contribute along with its antiinflammatory activity, towards the treatment of arthritic diseases.