Acute pancreatitis (AP) is acute inflammation of pancreas. The incidence of AP was 73 per 100,000 in Finland, including 70% of alcoholic and 20% of gallstone origin (Pelli et al. 2000, Pelli et al. 2008, Nordback et al. 2009). The diagnosis of the disease is based on the history of alcohol abuse and gallstone disease, the presence of symptoms with elevated amylase and lipase levels and confirmed by imaging investigations (Whitcomb 2006, Frossard et al. 2008).

Currently there is no specific therapy for AP, except for supportive or preventive treatment (Frossard et al. 2008). Generally the most accepted pathogenesis initiating AP is based on the discovery that the activation of trypsin in pancreatic acinar cells is the first step in the evolution of AP (Foitzik et al. 1994, Saluja et al. 1997, Hofbauer et al. 1998, Saluja et al. 1999). The associated genetic mutations are also found in several clinical investigations (Creighton et al. 2000, Felley et al. 2004, Frossard et al. 2008, Rebours et al. 2009). Besides trypsin activation, the following inflammatory cascades, such as release of cytokines, nitric oxide, reactive oxygen species and arachidonic acid metabolites, are believed to play important roles in the development of AP (Vollmar et al. 1989, Tsuji et al. 1994, Al-Mufti et al. 1998, Lundberg et al. 2000,).

Recently several studies have shown that experimental AP was induced by the over-activation of polyamine catabolism in transgenic rats (Alhonen et al. 2000, Hyvönen et al. 2006). Physiologically, polyamines are essential components for cellular survival and functions and very important in maintaining the integrity of pancreas (Alhonen et al. 2000). Furthermore, the use of polyamine analogues can ameliorate experimental AP in transgenic rats (Räsänen et al. 2002, Hyvönen et al. 2006).

The aim of the present dissertation is to investigate the role of polyamine catabolism in experimental taurodeoxycholate-induced and human AP by administering polyamine analogue bismethylspermine (Me2Spm).