pd-124966 and Inflammation

L-156,602, a C5a receptor antagonist, was found as an immunosuppressant with preferential effects on delayed-type hypersensitivity (DTH) in our screening program and it was shown that L-156,602 suppressed the efferent phase of DTH. Here, we tested its effects on experimental models of inflammation induced in mice. L-156,602 did not suppress serotonin- and carrageenan- induced inflammation while it completely suppressed concanavalin A-induced inflammation 4 h after elicitation. The inflammation appeared 24 h after the elicitation with concanavalin A and it was significantly suppressed by L-156,602. Muramyl dipeptide (MDP)-induced acute joint inflammation was also significantly suppressed by L-156,602. These results demonstrated the unique immunomodulating properties of L-156,602 in mouse experimental models of inflammation.

Topics: Animals; Carrageenan; Complement C5a; Concanavalin A; Female; Inflammation; Mice; Mice, Inbred BALB C; Mice, Inbred Strains; Mice, Nude; Mice, SCID; Peptides, Cyclic; Receptor, Anaphylatoxin C5a; Receptors, Complement; Serotonin