Implication of glucocorticoid in anti-inflammatory effects of Ro5-4864 in mouse pleurisy induced by carrageenan.
Mouse pleurisy induced by carrageenan is used to determine the mechanism of anti-inflammatory action of 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2-H-1,4-benzodiazepin-2 (Ro5-4864). Pre-treatment with Ro5-4864 inhibits different inflammatory parameters, such as neutrophil influx, MPO activity and NO levels in the early phase (4 h), as well as mononuclear cells and ADA activity in the late phase (48 h) of pleurisy. dl-Aminoglutethimide, inhibitor of steroidal synthesis, reverted the effect of Ro5-4864 on these different inflammatory parameters. Our results suggest that anti-inflammatory action of Ro5-4864 may be partly due to its capacity to inhibit leukocyte migration, as well as leukocyte activation and formation of NO by a mechanism dependent on glucocorticoids.
Farges
Roseli Coimbra
RC
Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, 88040-970 Florianópolis, SC, Brazil. roseli.farges@wanadoo.fr
da Silva
Marcelo Barreto Spillere
MB
Fröde
Tânia Silvia
TS
D000243:Adenosine Deaminase / Q000378:metabolism; D018663:Adrenergic Agents / Q000494:pharmacology; D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001570:Benzodiazepinones / Q000627:therapeutic use*; D002351:Carrageenan / Q000633:toxicity*; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
D018663:Adrenergic Agents; D000893:Anti-Inflammatory Agents; D001570:Benzodiazepinones; D005938:Glucocorticoids; D000616:Aminoglutethimide; C028513:4'-chlorodiazepam; D009569:Nitric Oxide; D002351:Carrageenan; D009195:Peroxidase; D000243:Adenosine Deaminase