Administration of anti-Reg I and anti-PAPII antibodies worsens pancreatitis.
BACKGROUND
The regeneration protein family (Reg), which includes Reg I and PAPII, is expressed in pancreas acinar cells, and increases in acute pancreatitis. We have demonstrated that Reg gene knockdown worsens severity of acute pancreatitis in the rat and hypothesize that the proteins offer a protective effect in this disease.


OBJECTIVE
We investigated the ability of anti-Reg and anti-PAP antibody to neutralize pancreatic Reg protein and affect pancreatitis severity.


METHODS
Pancreatitis was induced in rats by retrograde ductal injection of 4% sodium taurocholate.


METHODS
Eighty-four rats: 48 with induced pancreatitis, 30 sham operated, and 6 normal animals.


METHODS
Intraductal anti-Reg I and/or anti-PAPII antibody was administered at induced pancreatitis and sham operated subgroups of 6 rats each.


METHODS
Serum and pancreata were harvested 24 and/or 48 hours later and assessed for pancreatitis severity by pancreatic wet weight, serum C-reactive protein (CRP), amylase, PAPII levels, and histopathology.


RESULTS
Animals induced with pancreatitis with administration of anti-Reg/PAP antibodies had significantly higher wet weights compared with taurocholate and histopathological analysis revealed that anti-Reg/PAP treated animals had worse tissue inflammation and necrosis compared with controls. Serum CRP, amylase, and Reg levels did not significantly differ between experimental and sham control groups.


CONCLUSIONS
Administration of anti-Reg/PAP antibody worsened taurocholate-induced organ specific pancreatitis. These data suggest that the Reg family of proteins is protective in acute pancreatitis.
Viterbo
Domenico
D
Department of Surgery, SUNY Downstate Medical Center, Brooklyn, NY, USA.
Callender
Gordon E
GE
DiMaio
Theresa
T
Mueller
Cathy M
CM
Smith-Norowitz
Tamar
T
Zenilman
Michael E
ME
Bluth
Martin H
MH
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D000915:Antibody Affinity; D000951:Antigens, Neoplasm / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D007167:Immunotherapy / Q000009:adverse effects; D037181:Lectins, C-Type / Q000276:immunology*; D051847:Lithostathine / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D010195:Pancreatitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D000073718:Pancreatitis-Associated Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid
D000906:Antibodies; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D051847:Lithostathine; D000073718:Pancreatitis-Associated Proteins; C497616:Reg1a protein, rat; D013656:Taurocholic Acid