Treatment with active site inhibited factor VIIa - effects on inflammation in experimental acute pancreatitis
AbstractObjective: In critical illness, e.g. severe acute pancreatitis (SAP), an extensive cross-talk between inflammation and coagulation seems to exist. In previous studies in rats with SAP, we have demonstrated an anti-inflammatory effect following pre-treatment with active-site inhibited factor VIIa (fVIIai). In the current experiment the effect of treatment with fVIIai is studied, i.e fVIIai administered first after the induction of SAP in rats. Material and methods: AP was induced by infusion of taurodeoxy-cholic acid (5%) into the common bile duct. FVIIai was administered 30 min and 90 min, respectively, after the onset of AP. One group received no treatment. Non-operated and sham-operated rats were used as controls. The effect was evaluated after 6 hours by myeloperoxidase (MPO)-content in the lungs, ileum and pancreas, and by plasma levels of interleukin (IL)-6 and macrophage inflammatory protein (MIP)-2. The effect on coagulation was measured by PT, APTT, D-dimer and fibrinogen.
Results: In rats receiving fVIIai 30 min after induction of AP, MPO-levels were significantly lower in the lungs, and plasma concentrations of MIP-2 showed a trend towards reduction as compared to non-treated rats with AP. There was also a tendency towards lower IL-6 levels in plasma. No effect was seen on MPO-levels when fVIIai was given after 90 min, but there was a tendency towards lower MIP-2 and IL-6 levels. MPO in the ileum was low in all groups. MPO levels in the pancreas were not affected by treatment. Conclusions: Active site-inactivated factor VIIa, administered as early treatment after induction of taurodeoxycholate-induced AP in rats, seems to possess anti-inflammatory effects, reflected by a reduction of the influx of neutrophils in the lungs, and a tendency towards reduced plasma levels of MIP-2 and IL-6. These effects were less evident when fVIIai was administered later on during the course of disease.