Expression of Tumor Necrosis Factor-α, Interleukin-6, and Interferon-γ in Spontaneous Chronic Pancreatitis in the WBN/Kob Rat

Abstract

To clarify the pathophysiological significance of cytokines in chronic pancreatitis (CP), we analyzed tissue expressions of various cytokines in the onset and progression of spontaneous CP in the WBN/Kob rat. Four-week-old male WBN/Kob rats were fed a special pellet diet (MB-3) for 20 weeks, and 6 rats were killed every 4 weeks. Pathologically, CP occurred at 12 weeks and progressed thereafter. The inflammation and fibrosis peaked at 12 and 16 weeks, respectively. By semiquantitative reverse transcription-polymerase chain reaction, the expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and interferon (IFN)-gamma mRNAs peaked at 8, 12, and 16 weeks, respectively. Immunohistochemistry showed IL-6 expression in infiltrating inflammatory cells and vascular endothelial cells, whereas TNF-alpha was expressed in both acinar and infiltrating cells. IFN-gamma was localized to acinar, infiltrating and ductal cells, and its expression intensity showed significant correlation with those of fibrosis, type III collagen and alpha-smooth muscle actin. The in situ hybridization results were consistent with the RT-PCR data. These results suggest that tissue expressions of TNF-alpha and IL-6 are involved in the onset of pancreatitis and that IFN-gamma expression is related to the progression of CP.

Significant alterations of serum cytokine levels in patients with Peyronie's disease

“…The mRNA of both IFN-γ and IL-6 mRNA were elevated for liver specimens of a transgenic mouse model for chronic hepatitis C-virus liver disease. In spontaneous chronic pancreatitis in a rat model, IFN-γ was related to the progression of chronic pancreatitis (11). These findings are in agreement with the significantly increased IFN-γ serum levels detected in our series of PD patients.…”

“…They are well known to be involved in many fibrotic diseases (Table-3) of lung, liver, kidney, pancreas, and systemic aggressive fibromatosis as well as colloid and hypertrophic scar formation (8)(9)(10)(11)(12)(13). With the exception of a reported series from our group including a smaller patient population (14) to our knowledge there have been no further investigations of serum cytokine levels in PD.…”

“…Tissue mRNA expression of IL-6 in patients not only with acute but also with chronic viral hepatitis, was slightly elevated (8,23). In a rat model for chronic pancreatitis IL-6 tissue expression was able to be established (11). IL-6 gene polymorphism led to an increased number of chronic fibrotic lung diseases in transplanted patients (26).…”

“…In the airways of CF patients significantly elevated levels of circulating proinflammatory cytokines, in particular TNF-α have been reported (24). Other pulmonary diseases harboring diffuse fibrotic alterations like idiopathic pulmonary fibrosis, adult respiratory distress syndrome, lung cancer and chronic pancreatitis have revealed elevated TNF-α levels (9,11). In serum of patients with severe chronic hepatitis and liver cirrhosis significantly higher TNF-α levels were found compared to healthy controls, whereas patients with mild chronic hepatitis did not exhibit such alterations.…”

Serum TNF-Alpha Levels in Acute and Chronic Pancreatitis

“…Szuster-Ciesielska et al observed increased TNF-alpha and IL-6 levels in alcoholic liver cirrhosis and chronic pancreatitis (18). To clarify the pathophysiological significance of cytokines in chronic pancreatitis, Xie et al analyzed tissue expressions of various cytokines in the onset and progression in rats with chronic pancreatitis and their results suggested that tissue expressions of TNF-alpha and IL-6 were involved in the onset of pancreatitis and that IFN-gamma expression was related to the progression of chronic pancreatitis (19).…”