Complement inhibition by soluble complement receptor type 1 fails to moderate cerulein-induced pancreatitis in the rat.
CONCLUSIONS
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 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 micrograms initially, then 50 micrograms/kg). Six of these animals received hourly i.v. sCR1 (15 mg/kg, a proven complement-inhibiting dose in rats) and the other seven received i.v. saline. In parallel, 12 additional rats received hourly s.c. and i.v. 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) (all p < 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 a alveolar lavage to serum ratio of labeled albumen (0.041:0.121) both p < 0.05). Neither were changed by sCR1 treatment.
Weiser
M R
MR
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
Gibbs
S A
SA
Moore
F D
FD
Hechtman
H B
HB
D000208:Acute Disease; D000410:Alanine Transaminase / Q000378:metabolism; D000681:Amylases / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers; D002108:Ceruletide / Q000633:toxicity*; D003167:Complement Activation / Q000502:physiology; D003169:Complement Inactivator Proteins / Q000502:physiology*; D005765:Gastrointestinal Agents / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009929:Organ Size; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011951:Receptors, Complement / Q000502:physiology*
D015415:Biomarkers; D003169:Complement Inactivator Proteins; D005765:Gastrointestinal Agents; D011951:Receptors, Complement; D002108:Ceruletide; D009195:Peroxidase; D000410:Alanine Transaminase; D000681:Amylases