TREATMENT OF IFN-GAMMA TRANSGENIC MICE WITH ANTI-IFN-GAMMA REVEALS THE REMODELING CAPACITY OF THE ADULT PANCREAS

Pancreatic expression of gamma-interferon (IFN-gamma) initiates a casc ade of pathogenic changes that include pancreatic inflammation, islet cell destruction, hyperglycemia, and islet regeneration. In this study , we explore the developmental plasticity of the adult pancreas and pa rticularly its ability to return to normoglycemia and to remodel itsel f from an advanced pathogenic state. This was approached by treating a dult transgenic mice with a pulse of anti-IFN-gamma antibody and deter mining the functional and morphological status of the pancreas. We dem onstrated that anti-IFN-gamma antibody administration led to the reduc tion of hyperglycemic blood glucose levels in transgenic mice. We also observed that the pancreas returned from a profoundly perturbed state toward normality. Analysis of the mitotic index indicated that cell p roliferation previously associated with islet cell regeneration was gr eatly reduced after anti-IFN-gamma administration. Our results highlig ht the ability of the adult pancreas to remodel itself and return hom a complex pathological state to normalcy once the trophic signal induc ing this pathology is removed. These data also suggest that anti-IFN-g amma administration may have important clinical implications for treat ment of chronic pancreatitis in humans.