Enhanced expression of interleukin-18 in serum and pancreas of patients with chronic pancreatitis.

Aim: To investigate interleukin-18 (IL-18) in patients with chronic panreatitis (CP).

Methods: We studied 29 patients with CP and 30 healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated and incubated with 50 mmol/L ethanol, lipopolysaccharide (LPS) (doses 25 g/L, 250 g/L, 2500 g/L) and both agents for 24 h. Levels of IL-18 in the supernatants, and levels of IL-18, IL-12, interferon (IFN)-gamma and soluble CD14 in the serum were analysed by ELISA technique. Expression of IL-18 in PBMC was investigated by reverse-transcription (RT)-PCR. IL-18 protein levels in CP tissue and in normal pancreas were studied by ELISA technique. IL-18 levels in PBMC and pancreatic tissue were determined by Western blot. Immunohistochemistry for pancreatic IL-18 expression was performed.

Results: In patients, IL-18 serum levels were significantly enhanced by 76% (mean: 289.9+/-167.7 ng/L) compared with controls (mean: 165.2+/-43.6 ng/L; P<0.0005). IL-12 levels were enhanced by 25% in patients (18.3+/-7.3 ng/L) compared with controls (14.7+/-6.8 ng/L, P=0.0576) although not reaching the statistical significance. IFN-gamma and soluble CD14 levels were not increased. In vitro, LPS stimulated significantly and dose-dependently IL-18 secretion from PBMC. Incubation with ethanol reduced LPS-stimulated IL-18 secretion by about 50%. The mRNA expression of IL-18 in PBMC and the response of PBMC to ethanol and LPS was similar in CP patients and controls. In PBMC, no significant differences in IL-18 protein levels were detected between patients and controls. IL-18 protein levels were increased in CP tissues compared to normal pancreatic tissues. IL-18 was expressed by pancreatic acinar cells and by infiltrating inflammatory cells within the pancreas.

Conclusion: IL-18 originates from the chronically inflammed pancreas and appears to be involved in the fibrotic destruction of the organ.