Immunosuppressory activity of an isoxazolo[5,4-e]triazepine-compound RM-33 II. Effects on the carrageenan-induced inflammation.
The aim of this investigation was to evaluate effectiveness of RM-33, a new isoxazolotriazepine, in the model of carrageenan-induced inflammation in rats. Wistar rats were pretreated with intraperitoneal (ip) or oral (po) doses of RM-33, at daily doses ranging from 250 to 1000 microg, administered 1-3 days before elicitation of the carrageenan reaction. We showed that both routes of RM-33 administration were effective in significantly diminishing the footpad edema. The effects were dose-dependent and better pronounced at the ip administration of the compound. We found a lower production of tumor necrosis factor alpha (TNF-alpha) by mitogen-stimulated splenocytes isolated from rats pretreated with RM-33 and injected with carrageenan, as well as lower serum TNF-alpha levels in these rats, as compared to the respective control. Histological analysis of the skin reaction site revealed that in the rats pretreated with RM-33, the carrageenan-induced inflammation was reduced, as reflected by a lesser damage of mast cells, smaller infiltration by macrophages and a diminished edema of the connective tissue. Together with our previous data, indicating the antagonistic action of RM-33 in the adjuvant-induced footpad inflammation in mice, the present results confirm the anti-inflammatory activity of RM-33 compound.
Zimecki
Michał
M
Laboratory of Immunobiology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, PL 53-114 Wrocław, Poland. zimecki@iitd.pan.wroc.pl.
Ryng
Stainsław
S
Maczyński
Marcin
M
Chodaczek
Grzegorz
G
Kocieba
Maja
M
Kuryszko
Jan
J
Kaleta
Katarzyna
K
D000284:Administration, Oral; D000818:Animals; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology*; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D005260:Female; D005528:Foot / Q000473:pathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D007555:Isoxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001381:Azepines; D007166:Immunosuppressive Agents; D007555:Isoxazoles; C506874:RM 33 compound; D014409:Tumor Necrosis Factor-alpha; D002351:Carrageenan