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.