Control of serum cytokines and IL-1β, IL-10 mRNA in the pancreas with an acute pancreatitis model in rats. – effect of FR167653 – *
Acute pancreatitis is characterized by cytokine storms, which cause systemic inflammatory response syndrome（SIRS）and multiple organ failure（MOF）clinically. The effectiveness of FR167653（FR）, an inhibitor of IL-1 and TNF, for the control of cytokine storms was investigated in an acute pancreatitis model in rats. Acute pancreatitis was induced in rats with a closed duodenal loop model（CDL）. Serum amylase and lipase concentrations, serum IL-1β, IL-6 and IL-10 concentrations, and IL-1β, IL-10 mRNA expression in the pancreatic tissue were evaluated in a CDL group（n＝６）, an FR treatment（CDL＋FR）group（n＝６）and a sham group（n＝６）. To determine the outcome regarding the control of cytokine storms, histological findings at 2, 4 and 6h after induction of acute pancreatitis were investigated. １）The CDL＋FR group showed lower serum amylase and lipase concentrations 2 and 4h after the induction of acute pancreatitis.２）The CDL＋FR group showed a lower serum IL-1β concentration 6h after the induction of acute pancreatitis. ３）The CDL＋FR group showed a lower serum IL-6 concentration 2 and 4h after the induction of acute pancreatitis. ４）A rise in serum IL-10 concentrations was observed in the CDL group and the CDL＋FR group, but it was a little lower than in the CDL＋FR group. ５）There was also a rise in the expression of IL-1β mRNA in the pancreas in both the CDL group and the CDL＋FR group. This decreased faster in the CDL＋FR group as time passed. ６）The expression of IL-10 mRNA in the pancreas rose in both the CDL group and the CDL＋FR group, but it was higher in the CDL＋FR group 2h after the induction of acute pancreatitis. Expression in the CDL＋FR group decreased faster as time passesd. ７）Less histological damage（vacuolization and necrosis）was observed in the pancreas in the CDL＋FR group. These results suggested that FR167653 reduces the production of inflammatory cytokines and inhibits the development of a severe cytokine storm and pancreatitis. (Accepted on October 12，2004）
