Effects of glucocorticoids in the L-arginine-induced acute pancreatitis: the mechanism of NF-KB activation

Introduction: The effects of glucocorticoids on acute pancreatitis (AP) have remained contradictory. The aims of the present study were 1. to investigate the consequences of an exogenous glucocorticoid agonist (methylprednisolone – MP) and a glucocorticoid antagonist (RU-38486– RU) treatment on local and systemic responses to L-arginine-induced acute pancreatitis in rats, and 2. to gain an insight into the role of NF-κB activation and macrophage inhibitory factor (MIF) release in glucocorticoid action.

Materials and Methods: Male Wistar rats weighing 250–300g were used. Acute pancreatitis was induced by intraperitoneal administration of L-arginine (2×250mg/100gr b.w.). MP (30mg/kg b.w. s.c.) and RU (5mg/kg b.w. s.c.) treatment was started just 1 hour before L-arginine injection. Rats were sacrificed by abdominal aorta exsanguinations 0, 8, 12, 24h following pancreatitis induction. Serum amylase activity, IL-6 with bioassays, pancreatic weight/body weight (pw/bw), NF-κB activation, histology and serum MIF level were examined.

Results: We demonstrated that L-arginine induces pancreatitis resulting NF-κB activation and consecutive proinflammatory cytokine release in rats. In MP-treated group the amylase level and the IL-6 activity significantly decreased as compared to the non-treated and RU-treated groups. The glucocorticoid treatment significantly decreased the level of NF-κB activation 24h following AP inductions. The glucocorticoid antagonist treatment resulted significantly higher MIF production at 8 and 12h following L-arginin injection as compared to the MP-treated and non-treated groups.

Conclusion: These findings suggest that the glucocorticoid dependent mechanisms play an important role in the control of systemic inflammatory response in L-arginine-induced experimental pancreatitis.