Complement inhibition by soluble complement receptor type 1 fails to moderate cerulein-induced pancreatitis in the rat

Weiser, Martin R.; Gibbs, Simon A. L.; Moore, Francis D.; Hechtman, Herbert B.

CONCLUSION: Cerulein-induced pancreatitis in rats associated with remote liver and lung dysfunction. Soluble complement receptor 1 (sCR1) does not reduce the local or remote injury. Thus complement activation does not moderate cerulein-induced pancreatitis or the associated liver and lung injury. BACKGROUND: The local and remote injury of pancreatitis resembles other inflammatory events that are mediated by complement. This study examines the effect of complement inhibition with sCR1 in cerulein-induced pancreatitis in rats. METHODS: Thirteen Sprague-Dawley rats received five hourly subcutaneous doses of cerulein (100 μg initially, then 50 μg/kg). Six of these animals received hourly iv sCR1 (15 mg/kg, a proven complement-inhibiting dose in rats) and the other seven received iv saline. In parallel, 12 additional rats received hourly sc and iv saline. RESULTS: Compared to saline controls, rats receiving cerulein showed increased pancreatic wet-to-dry ratio (3.25∶8.52) hematocrit (40 to 47%), ascites volume (2.1 to 6.1 mL), serum amylase (1680 to 10,700 U/L), and ascites amylase (32,200 to 167,000 U/L) (allp<0.05). None of these parameters were modified by treatment with sCR1. Serum SGPT, which increased from 33.4 to 46.6 U/L in cerulein-infused rats, showed a trend toward reduction to 38.8 U/L in rats treated with sCR1. Cerulein-treated rats also had increased lung myeloperoxidase (0.069 to 0.097 U/g) and lung permeability, as assessed by alveolar lavage to serum ratio of labeled albumen (0.041∶0.121) (bothp<0.05). Neither were changed by sCR1 treatment.