Inhibitory mechanisms of highly purified vitamin B2 on the productions of proinflammatory cytokine and NO in endotoxin-induced shock in mice.
Inhibitory effects of highly purified vitamin B2 (riboflavin-5'-sodium phosphate, >97%) on the interleukin (IL)-6, macrophage inflammatory protein (MIP)-2 and nitric oxide (NO) in LPS-induced shock mice were evaluated. Vitamin B2 at 20 mg/kg (protective effect on mice mortality induced by LPS), intravenously administered 6 h after LPS injection, significantly decreased the plasma elevated levels of IL-6 and MIP-2 at 9 and 12 h. In addition, vitamin B2 lowered the tissue concentration and the mRNA expression of IL-6 in lung and those of MIP-2 in liver at 9 h. Vitamin B2 also reduced concentration of MIP-2 concentration in lung, and inhibited mRNA expression in kidney, respectively. Vitamin B2 decreased the plasma elevated NO levels in accordance with a reduction in expression of inducible NO synthase (iNOS) both at 21 and 24 h. Accordingly, the reduction in elevated plasma cytokine levels and NO based on the inhibitory effect on local cytokine mRNA expression and iNOS would be responsible for the anti-septic effect of vitamin B2.
Kodama
Kohtarou
K
Tsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan. k-kodama@hhc.eisai.co.jp
Suzuki
Mamoru
M
Toyosawa
Toshio
T
Araki
Seiichi
S
D000818:Animals; D015153:Blotting, Western; D054426:Chemokine CXCL2; D016207:Cytokines / Q000096:biosynthesis*; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015846:Monokines / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012256:Riboflavin / Q000494:pharmacology*; D012772:Shock, Septic / Q000378:metabolism*; D014815:Vitamins / Q000494:pharmacology*
D054426:Chemokine CXCL2; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D015846:Monokines; D012333:RNA, Messenger; D014815:Vitamins; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D012256:Riboflavin