Therapeutic Effect of an Immunomodulator on Pancreatic Endocrine Secretion Disorder and Insulitis in an Animal Model of Autoimmune Pancreatitis

Abstract

Adrenocortical hormones are effective in many, but not all, cases of autoimmune pancreatitis （AIP）. While effective treatment for refractory and recurrent cases of AIP has not been established, immunomodulators are sometimes used. We examined the therapeutic effect of the immunomodulator FK506 against AIP using an animal model: aly/aly male mice. Mice were divided into three groups based on FK506 dose: 1mg/kg, 2mg/kg, and non-administration （pancreatitis） groups. Pancreatic exocrine gland injury was regarded as pancreatitis and pancreatic endocrine injury was regarded as insulitis. Histological evaluation of pancreatic tissue at 16 and 24 weeks of age was performed quantitatively using ImageJ software, and the three groups were compared. The pancreatitis group developed pancreatitis at 24 weeks of age, but onset of pancreatitis was suppressed in the 1mg group. However, pancreatitis development was not suppressed in the 2mg group, and pancreatitis developed from as early as 16 weeks of age. In the pancreatitis group, insulitis resulted in morphological changes such as shrinkage of pancreatic islets of Langerhans as inflammatory cell infiltration into pancreatic acinar cells became stronger. No significant difference was observed between the 1mg group and the pancreatitis group in the islet area but, in the 2mg group, there was significant reduction in area compared to the pancreatitis group and the 1mg group. Although administration of FK506 at a low dose had an effect of suppressing the onset of pancreatitis, administration at a higher dose appeared to exacerbate pancreatitis.