Eme-ossigenasi 1 (HO-1) e citochine proinfiammatorie: ruolo della biliverdina

HO-1 acts as a protective gene by virtue of her anti-inflammatory, antiapoptotic and anti-proliferative actions and catalyzes the rate-limiting step in heme metabolism that produces biliverdin (BV), carbon monoxide (CO) and iron (1). Our previous study shows that CO pretreatment prevents endotoxic shock respiratory derangements and ameliorates overall clinic outcome in a pig model of endotoxemia (2), but the role of BV and its potential use in preventing endotoxic shock had never been studied. This study was designed to explore putative protective functions of BV in LPS-induced TNF-a and IL-6 expression in a mice model of endotoxic shock. In order to find the proper dose/administration of LPS, in terms of TNF-a expression, 60 C57BL6 mice were randomly divided in 5 groups, and treated, i.v. or i.p., with 0.3, 0.5 or 1 mg/kg of LPS. Then, 96 C57BL6 mice were randomly divided in 8 groups, and pre-treated, at different time point before LPS injection (1mg/kg, i.p.), with 50 or 200 mM/kg i.p. of biliverdin. TNF-a expression was evaluated after 1h of LPS administration, while IL-6 after 6 hrs. 10 animals, treated only with saline, served as sham group. Results showed that 2 hrs pretreatment with biliverdin highly significantly reduced TNF-a and IL-6 expression induced by LPS.