Anti-inflammatory effects and specificity of L-156,602: comparison of effects on concanavalin A and zymosan-induced footpad edema, and contact sensitivity response.
We investigated the in vivo selective anti-inflammatory effect of L-156,602, which was first identified as a preferential delayed-type hypersensitivity-suppressant in our screening program and first reported to be a C5a antagonist. The agent most profoundly suppressed footpad edema 4 h after elicitation by concanavalin A (con A) and also caused a significantly impaired response after a further 20 h. Footpad edema induced by either serotonin, carrageenan or zymosan was not much influenced by the agent. Although the dominant cell population that migrated in response to con A and zymosan 4 h after elicitation was neutrophils, L-156,602 specifically prevented the con-A-induced migration of neutrophils, suggesting a distinct mechanism of neutrophil recruitment between con A and zymosan-induced inflammation. The agent also reduced the contact-sensitivity response, especially in host mice sensitized with a moderate dose of picryl chloride and almost completely suppressed the infiltration of mononuclear leukocytes and neutrophils into the site of inflammation. These selective effects of L-156,602 on inflammatory reactions appeared to be not merely via C5a antagonism.
Tsuji
R F
RF
Noda Institute for Scientific Research, Chiba, Japan.
Yamakoshi
J
J
Uramoto
M
M
Koshino
H
H
Saito
M
M
Kikuchi
M
M
Masuda
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002351:Carrageenan / Q000633:toxicity; D015936:Complement C5a / Q000037:antagonists & inhibitors*; D003208:Concanavalin A / Q000633:toxicity; D003877:Dermatitis, Contact / Q000188:drug therapy*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D006614:Hindlimb / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D009504:Neutrophils / Q000187:drug effects; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010853:Picryl Chloride / Q000633:toxicity; D012701:Serotonin / Q000633:toxicity; D013047:Specific Pathogen-Free Organisms; D015054:Zymosan / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000903:Antibiotics, Antineoplastic; D010456:Peptides, Cyclic; C051485:PD 124966; D003208:Concanavalin A; D012701:Serotonin; D015936:Complement C5a; D002351:Carrageenan; D015054:Zymosan; D010853:Picryl Chloride