The importance of innate immunity in host defense is becoming clear after discovery of innate immune receptors such as Toll-like receptor or Nod-like receptor. Innate immune system plays an important role in diverse pathological situations such as autoimmune diseases. Role of innate immunity in the pathogenesis of metabolic disorders such as type 2 diabetes, metabolic syndrome or atherosclerosis that has not been previously considered as inflammatory disorders, is also being appreciated. Here, the role of innate immunity in the development of type 1 diabetes, a classical organ-specific autoimmune disease, and type 2 diabetes will be discussed, focusing on the role of specific innate immune receptors involved in these disease processes.
Animals ; Cytokines/*immunology ; Diabetes Mellitus, Type 1/*immunology ; Diabetes Mellitus, Type 2/*immunology ; Humans ; Immunity, Innate/*immunology ; Inflammasomes/*immunology ; *Models, Immunological ; Pancreas/immunology

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Castleman Disease ; immunology ; pathology ; Cyclophosphamide ; therapeutic use ; Diagnostic Errors ; Doxorubicin ; therapeutic use ; Humans ; Immunoglobulin G ; blood ; Kidney ; Lymph Node Excision ; Lymph Nodes ; pathology ; surgery ; Lymphatic Diseases ; drug therapy ; immunology ; pathology ; surgery ; Male ; Middle Aged ; Nephrectomy ; Pancreas ; Plasma Cells ; immunology ; pathology ; Prednisone ; therapeutic use ; Submandibular Gland ; Vincristine ; therapeutic use

OBJECTIVETo investigate clinicopathological features of fibrous mass-forming chronic pancreatitis (FMCP), to compare clinicopathological and immunohistochemical characteristics between autoimmune pancreatitis (AIP) and fibrous mass-forming non-autoimmune pancreatitis (nAIP) and to provide evidence for pathological diagnosis, differential diagnosis and clinical treatment strategy.

METHODSClinicopathological features were analyzed in 81 cases of FMCP. Infiltrating IgG4(+) plasmacytes were counted by immunohistochemical staining.

RESULTSAmong 81 cases of FMCP, 20 cases were diagnosed as AIP and 61 cases were interpreted as nAIP. AIP was more common in males over 50 years, whereas nAIP was seen in much younger patients (P = 0.001). The amount of inflammatory cells in the stroma of AIPs was remarkable higher than that in nAIPs (P = 0.002). The incidence of neuritis in AIPs (100%, 20/20) was also higher compared with that of nAIPs (75.4%, 46/61; P = 0.017). Storiformed-fibrosis was more common in AIPs (95.0%, 19/20) than in nAIPs (1.6%, 1/61;P = 0.000). Pancreatic intraepithelial neoplasia (PanIN) was observed in 50.0%(10/20) of AIPs and 32.8%(20/61) of nAIPs, with a greater severity observed in AIPs (P = 0.031). Tubular complex (TC) was more commonly observed in AIPs (65.0%, 13/20) than nAIPs (26.2%, 16/61;P = 0.002). Among 81 cases of FMCP, 61 cases had less than 11 IgG4(+) plasmacytes /HPF, 7 cases had 10-30/HPF and 13 cases had over 30/HPF.

CONCLUSIONSFMCPs include both AIP and nAIP. AIP has distinct pathological features and the presence of IgG4(+) plasmacyte is an important diagnostic parameter. FMCP appears to be an important precancerous lesion of pancreatic ductal adenocarcinoma. Surgery may be considered for patients with FMCP due to its mass-forming nature. In contrast, patients with AIP are treated medically due to its steroid-responsiveness. Therefore, accurate and timely diagnosis of AIP is of clinical relevance to avoid unnecessary surgical complications and to prevent progression of the disease.

Adult ; Aged ; Autoimmune Diseases ; immunology ; pathology ; surgery ; Carcinoma, Pancreatic Ductal ; immunology ; pathology ; surgery ; Diagnosis, Differential ; Female ; Fibrosis ; Humans ; Immunoglobulin G ; metabolism ; Male ; Middle Aged ; Pancreas ; pathology ; Pancreatic Neoplasms ; immunology ; pathology ; surgery ; Pancreatitis, Chronic ; immunology ; pathology ; surgery ; Plasma Cells ; immunology ; Precancerous Conditions ; immunology ; pathology ; surgery ; Young Adult

Autoimmune pancreatitis (AIP) has two distinct subsets. Type 1 AIP or lymphoplasmacytic sclerosing pancreatitis is systemic disease with the elevation in serum levels of the IgG4. Type 2 AIP, also called duct-centric pancreatitis, features granulocyte epithelial lesions with duct obstruction in the pancreas without systemic involvement. Here, we report a case of type 2 AIP diagnosed by pathology, which is the first report in Korea. The case is a 56-year-old woman who presented with anorexia and vomiting. Computed tomography revealed mass-like lesion in the pancreatic head and the compression of the distal common bile duct and the head portion of the main pancreatic duct. Serum levels of the IgG4 were normal. Histologic examination revealed a dense neutrophil infiltration in the pancreatic parenchyme associated with extensive fibrosis, thereby confirming the diagnosis of type 2 AIP. The abnormalities in the clinical, laboratory, and radiological findings improved after oral steroid treatment.
Autoimmune Diseases/blood/immunology/*pathology ; Female ; Fibrosis ; Humans ; Immunoglobulin G/blood ; Magnetic Resonance Imaging ; Middle Aged ; Neutrophils/immunology ; Pancreas/pathology ; Pancreatitis/*drug therapy/immunology/pathology ; Steroids/*therapeutic use ; Tomography, X-Ray Computed

BACKGROUNDLarge animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to establish Chinese Guizhou minipig models with streptozotocin (STZ)-induced diabetes and characterize the animal models by analyzing inflammatory cytokine levels in aortic wall, such as tumor necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta) and interleukin-6 (IL-6).

METHODSTwenty-two male Chinese Guizhou minipigs (age, 4 to 6 months; weight, 20 kg to 30 kg) were divided into STZ-induced diabetic group (n = 12) and control group (n = 10). STZ (125 mg/kg) was administrated to induce hyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol/L. Oral glucose tolerance test (OGTT) was performed before and one month after STZ administration and serum concentrations of alanine transaminase, asparagine transaminase, albumin, blood urea nitrogen, creatinine, lipids and white blood cell count were measured before and six months later. Animals in both groups were euthanized after six months and pancreas was examined immunohistochemically for islet beta cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-alpha level in tissue conditioned medium by Western blot. TNF-alpha, IL-1beta and IL-6 mRNA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction (RT-PCR).

RESULTSSignificant elevation in serum glucose levels was observed one month and six months after STZ induction (P < 0.001) and markedly increased OGTT values were noted, compared with baseline data. The normal pancreas had many irregular sized islets and small clusters of islet beta cells, while in pancreas of diabetic minipigs islet beta cells almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Western blot demonstrated dramatically increased TNF-alpha level in aotic intima conditioned medium, and significant elevation of TNF-alpha, IL-1beta and IL-6 mRNA levels was revealed by RT-PCR.

CONCLUSIONSThe present study has established Chinese Guizhou minipig models with STZ-induced diabetes. Inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) significantly elevated in aortic intima of diabetic minipigs.

Animals ; Aorta ; chemistry ; Diabetes Mellitus, Experimental ; immunology ; pathology ; Glucose Tolerance Test ; Immunohistochemistry ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Male ; Pancreas ; pathology ; Streptozocin ; Swine ; Swine, Miniature ; Tumor Necrosis Factor-alpha ; blood

BACKGROUNDOne of the major causes of death in severe acute pancreatitis (SAP) is severe infection owing to bacterial translocation. Some clinical studies suggested that ecoimmunonutrition (EIN) as a new strategy had better treatment effect on SAP patients. But the experiment studies on the precise mechanism of the effect of EIN were less reported. In this study, we mainly investigated the effects of EIN on bacterial translocation in SAP model of dogs.

METHODSSAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in healthy hybrid dogs. The SAP dogs were supported with either parenteral nutrition (PN) or elemental enteral nutrition (EEN) or EIN. The levels of serum amylase, serum aminotransferase and plasma endotoxin were detected before and after pancreatitis induction. On the 7th day after nutrition supports, peritoneal fluid, mesenteric lymph nodes (MLN), liver, and pancreas were collected for bacterial culture with standard techniques to observe the incidence of bacterial translocation. Pathology changes of pancreas were analyzed by histopathologic grading and scoring of the severity of pancreas, and the degree of intestinal mucosal damage was assessed by measuring mucosal thickness, villus height, and crypt depth of ileum.

RESULTSCompared with PN and EEN, EIN significantly decreased the levels of serum amylase, serum aminotransferase, plasma endotoxin, and the incidence of bacterial translocation. Furthermore, compared with the others, the histology scores of inflammation in pancreas and the ileum injury (ileum mocosa thickness, villus height, and crypt depth) were significantly alleviated by EIN (P < 0.05). Moreover, concerning liver function, the serum levels of alanine aminotransferase, aspartate aminotransferase and albumin were ameliorating significantly in the EIN group.

CONCLUSIONOur results suggested that EIN could maintain the integrity of intestinal mucosal barrier and reducing the incidence of bacterial translocation in SAP dogs. Early EIN was safe and more effective treatment for SAP dogs.

Acute Disease ; Amylases ; metabolism ; Animals ; Bacteria ; isolation & purification ; Dogs ; Endotoxins ; blood ; Enteral Nutrition ; Immunity ; Intestinal Mucosa ; metabolism ; Liver ; physiopathology ; Nutritional Support ; Pancreas ; pathology ; Pancreatitis ; immunology ; metabolism ; therapy ; Parenteral Nutrition

OBJECTIVETo summarize the treatment experience of long-term surviving patients after combined abdominal organ transplantation.

METHODSFrom October 2001 to January 2005, 19 patients received combined abdominal organ transplantation in Nanfang Hospital, including 6 with simultaneous kidney-pancreas transplantation (SKPT), 12 with combined liver-kidney transplantation (CLKT), and 1 with simultaneous liver-pancreas transplantation (SLPT). The periods of follow up were from 6 months to 3 years and 8 months. Summarize primary diseases of the patients, factors which impacted on patients long-term survival rate, and immunological characteristics of combined abdominal organ transplantation.

RESULTSAll of 19 transplant cases were performed successfully. Among then, 18 were followed up; 16 survived till now; 2 patients undergoing liver-kidney transplantation were dead, one of which died from myocardial infarction in the 18 months after operation, and one died from cytomegalovirus in infection of lung in 13 months; 1 liver-kidney transplantation patient and 2 pancreas-liver transplantation patients experienced acute rejection once; 2 patients were found nephrotoxicity. Among the 18 patients, 4 patients' survival time were over 3 years, 7 over 2 years, 6 over 1 year, 1 over 10 months.

CONCLUSIONSCombined abdominal organ transplantation is effective for treatment of two abdominal organ failure diseases. Factors which impact on patients long-term surviving include choosing suitable recipient, high quality of donated organ, avoidance of surgical complication, the history of myocardial infarction before operation, immunosuppressive regime and virus infection late after transplantation. Combined abdominal organ transplantation has some different immunological characteristics from single organ transplantation.

Adult ; Aged ; Duodenum ; transplantation ; Female ; Follow-Up Studies ; Humans ; Kidney Transplantation ; immunology ; methods ; mortality ; Liver Transplantation ; immunology ; methods ; mortality ; Male ; Middle Aged ; Pancreas Transplantation ; immunology ; methods ; mortality ; Treatment Outcome

OBJECTIVETo analyze the clinical and laboratory features of anti-soluble liver antigen/liver-pancreas (SLA/LP) autoantibody positive patients with abnormal liver functions.

METHODSFrom July 1999 to August 2004, 4928 serum samples from patients with abnormal liver functions (ALT >40 U/L) were collected. A series of autoantibody examinations were carried out. Clinical manifestations and laboratory findings of 8 patients with anti-SLA/LP autoantibody positive were reviewed.

RESULTSAmong the 5500 serum samples, 8 cases (6 females and 2 males) with positive anti-SLA/LP autoantibodies were found with complete clinical information. The age of the patients was (27-76) years old. The case histories were from 2 years to 10 years. Of the 8 patients, 6 cases had liver cirrhosis and HBsAg-negative and anti-HCV-negative, active, 1 case had liver cirrhosis with HBsAg-positive, but HBVDNA negative; 1 case had liver cirrhosis and anti-HCV positive, but HCV RNA negative. The 8 cases were all ANA positive with titers of 31:320. Four cases were AMA positive and 2 among these 4 cases were M2 positive. The most frequent symptoms were fatigue, anorexia, nausea, jaundice, abdominal distention and edema of lower limbs. All patients had high hypergammaglobulinemia.

CONCLUSIONAnti-SLA/LP autoantibody was at a low detection rate in the study with females in preponderance, Clinical and laboratory characteristics of the 8 cases were consistent with those of the autoimmune hepatitis (AIH). Testing for anti-SLA autoantibodies helps in the diagnosis of AIH in many patients who may otherwise be misdiagnosed.

Adult ; Aged ; Autoantibodies ; immunology ; Autoantigens ; immunology ; Female ; Hepatitis, Autoimmune ; diagnosis ; immunology ; Humans ; Male ; Middle Aged ; Pancreas ; immunology ; Sequence Homology

BACKGROUND/AIMS: Autoimmune pancreatitis is a distinctive type of chronic pancreatitis with reversibility. We analyzed the largest number of patients with autoimmune pancreatitis among the studies carried out at a single institution in Korea. METHODS: We retrospectively analyzed the clinical, radiologic, laboratory and histologic features in 17 patients who were diagnosed as autoimmune pancreatitis. RESULTS: The patients were predominately elderly men who presented with jaundice or nonspecific gastrointestinal symptoms. In most of the patients, serum pancreatic enzymes were normal or mildly elevated with an accompanying cholestatic biochemical profile. Elevated IgG levels and detection of autoantibodies were observed in 47% (8/17) and 35% (6/17), respectively. Thirteen patients showed histologic findings of lymphoplasmacytic infiltration and fibrosis, and one patient showed predominant infiltration of eosinophils. Fifteen patients revealed radiologic images of diffuse swelling of pancreas and the sclerosing pattern on direct pancreatogram. All of the features improved in response to oral steroid therapy. Two cases showed focal narrowing with upstream duct dilatation and thus, they were diagnosed as focal type. Diabetes mellitus concurred in 13 cases and primary sclerosing cholangitis and Sjogren's syndrome were present in 1 case, respectively. CONCLUSIONS: The recognition of autoimmune pancreatitis allows patients to avoid unnecessary surgery and recover with the administration of oral steroid.
Aged ; Autoimmune Diseases/*diagnosis/pathology ; Chronic Disease ; English Abstract ; Humans ; Male ; Middle Aged ; Pancreas/pathology ; Pancreatitis/*diagnosis/immunology/pathology

OBJECTIVETo explore methods of preventing and reversing rejection after simultaneous pancreas-kidney transplantation (SPK).

METHODSSeventeen patients performed SPK operation from Sep, 1999 to Sep, 2003 were reviewed retrospectively. Immunosuppression was achieved by triple regimen consisting of cyclosporine, mycophenolate mofetil (MMF)/azathioprine and steroid. 2 patients were treated with Dalizumab, the other three patients used OKT3 as immune induction.

RESULTS1 patient experienced the accelerated rejection, the pancreas and kidney grafts were resected because of failure of conservative therapy. 8 patients experienced renal acute rejection, 2 cases suffered from pancreas acute rejection at the same time. All these patients received daily high dose pulse steroid for 3 days. OKT3 was administered in 2 patients with steroid resistance rejection. All the grafts were successfully rescued.

CONCLUSIONSReasonable application of immunosuppression after SPK operation and adoption of systemic measures which can reduce sensitivity of high risk receptor before SPK operation are the effective methods of preventing and treating rejection.

Administration, Oral ; Adult ; Azathioprine ; administration & dosage ; Cyclosporine ; administration & dosage ; Diabetic Nephropathies ; surgery ; Drug Therapy, Combination ; Female ; Glucocorticoids ; administration & dosage ; Graft Rejection ; prevention & control ; Humans ; Immunosuppressive Agents ; administration & dosage ; Kidney Transplantation ; immunology ; Male ; Middle Aged ; Pancreas Transplantation ; immunology ; Prednisolone ; administration & dosage ; Retrospective Studies ; Transplantation, Homologous