Effect of monoclonal antibodies to enteroglucagon on ileal adaptation after proximal small bowel resection

On the basis of circumstantial clinical and experimental evidence, it has been suggested that enteroglucagon (EG) may act as an enterotrophic factor. This study was undertaken to evaluate the effects of long term in vivo immunoneutralisation of EG, using monoclonal antibodies to EG, on the hyperplastic ileal response after small bowel resection. Nineteen rats had a 70% proximal resection. A group of 10 rats was given iv 0.5 ml of undiluted hybridoma ascites immediately after the operation and on the 7th day postoperatively. Furthermore 0.025 ml/day of the same hybridoma ascitic fluid was continuously delivered ip for 14 days via mini-osmotic pumps. The hybridoma ascites was prepared from the clone 23.6B4 synthesising a monoclonal antibody directed toward the N-terminal to central region of the glucagon molecule which showed a marked crossreaction with EG. A control group of 9 rats was given a corresponding amount of antibody-free plasmacytoma ascites (Ag 8.653) by the same technique. Seven and 14 days postoperatively there was a plasma anti-EG-antibody excess with an excess binding capacity of 84.9 glucagon eq nM and 88.5 glucagon eq nM respectively. The three dimensional architecture and the proliferative activity of the ileal remnant were evaluated two weeks postoperatively. Despite a continuous immunoneutralisation of circulating endogenous EG by monoclonal antibodies, the adaptive response of the ileal remnants was of the same magnitude as that seen in the control group. These data do not support the hypothesis that EG is a circulating enterotrophic regulatory peptide.