Modulation by conagenin of inflammatory mediator productions in mice given 5-fluorouracil.
The effect of conagenin (CNG) on the production of the inflammatory mediators induced by 5-fluorouracil (5-Fu) in mice was investigated. We found that the production of interleukin (IL)-1 alpha and prostaglandin E2(PGE2) in whole spleen cell cultures from mice given a sublethal dose of 5-Fu was induced in the week after treatment, and subsequently the production of IL-4 and IL-IO was induced. The administration of 5-Fu and CNG suppressed the production of IL-1 alpha and PGE2, and induced the production of IL-4 and IL-10 earlier than 5-Fu alone did. In cultures of cells from Peyer's patches, IL-1 alpha production was suppressed by CNG administration. The effect of CNG was also demonstrated in vitro. CNG at 0.001 to 1.0 microgram/ml suppressed IL-1 alpha and PGE2 production in cultures of adherent peritoneal exudate cells (PEC) and cells from Peyer's patches of mice given 5-Fu. IL-10 production in cultures of non-adherent splenic cells was enhanced by CNG. These results indicate that CNG modulates inflammatory responses induced by 5-Fu through production of anti-inflammatory cytokines such as IL-4 and IL-10.
Kawatsu
M
M
Insitute for Chemotherapy, M.C.R.F., Shizuoka, Japan.
Yamashita
T
T
Ishizuka
M
M
Takeuchi
T
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D005472:Fluorouracil / Q000633:toxicity*; D018836:Inflammation Mediators / Q000378:metabolism*; D051379:Mice; D012694:Serine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000964:Antimetabolites, Antineoplastic; D016207:Cytokines; D018836:Inflammation Mediators; C069645:conagenin; D012694:Serine; D015232:Dinoprostone; D005472:Fluorouracil