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We studied potential indicators of severe acute pancreatitis by measuring the blood concentrations of various cytokines, polymorphonuclear leucocyte elastase (PMN-E), acute phase reactants, pancreatic amylase (P-AMY), pancreatic elastase-1 (E-1) and white blood cell (WBC) counts in patients with acute pancreatitis. In addition, the presence of multiple organ damage was assessed. Subjects consisted of 22 patients with acute pancreatitis including severe (n = 11), moderate (n = 4) and mild (n = 7) cases. A significant positive correlation was observed between the number of organs damaged and the peak concentrations of interleukin (IL)-6, PMN-E, C-reactive protein (CRP) and pancreatic secretory trypsin inhibitor (PSTI). Among these markers, blood concentrations of PMN-E and IL-6 rapidly increased and peaked at the early phase of acute pancreatitis whereas CRP and PSTI did not. The elevation of PMN-E and IL-6 was greater the more severe the symptoms. However, no significant correlation was observed between the number of organs damaged and the maximum serum concentrations of P-AMY and E-1, or the WBC count, which have been considered to be markers of pancreatitis. These results suggest that PMN-E and IL-6 concentrations are useful indicators of severity and prognosis and their determination facilitates the selection of appropriate treatment in the early stages of disease to prevent the aggressive progression of acute pancreatitis. [ABSTRACT FROM AUTHOR]

Background/Aims: Non-occlusive mesenteric ischemia (NOMI) has been defined as diffuse intestinal ischemia that often results in intestinal gangrene in the presence of a patent arterial trunk. The prevalence and nature of NOMI in acute pancreatitis was investigated. Methods: A total of 120 consecutive patients with acute pancreatitis managed in the Department of Surgery II, Kumamoto University Medical School, from April 1992 through December 2002, were investigated retrospectively. Among them, 60 patients had the severe form. Results: The overall mortality of acute pancreatitis patients was 8.3% (10/120). The prevalence and mortality of acute pancreatitis associated with NOMI were 6.7% (8/120) and 63% (5/8), respectively, while those of patients with NOMI-associated intestinal gangrene were 4.2% (5/120) and 100% (5/5), respectively. The mortality of patients with severe acute pancreatitis who did not develop NOMI was 10% (5/52). All patients with NOMI-associated intestinal gangrene quickly progressed and subsequently died of multiple organ failure. Plasma creatine phosphokinase (CPK) and lactate levels were elevated significantly in patients with NOMI. Conclusion: Acute pancreatitis associated with NOMI was extremely severe. If the plasma CPK and lactate levels are extremely high, NOMI should be suspected. [ABSTRACT FROM AUTHOR]

We demonstrated the dynamic aspects of granulocyte activation in rat severe acute pancreatitis which was induced by cerulein and aggravated following lipopolysaccharide (LPS) injection. Pancreatitis induced by cerulein increased intracellular elastase activity of granulocytes in the blood. However, significant systemic cytokinemia was not provoked under such conditions. After induction of severe pancreatitis by LPS, intracellular elastase activity of circulating granulocytes decreased markedly and immediately. The timing of this decrease was concomitant with induction of systemic hypercytokinemia and granulocytes migration into the lung. Overall results provide the following implications: (1) circulating granulocytes are activated by the induction of mild pancreatitis; (2) the activation of granulocytes is mediated by other factors than systemic cytokinemia, such as locally produced cytokine; (3) those priming granulocytes immediately and significantly migrate from the circulation into extravascular space by the induction of endotoxemia; (4) the migration of granulocytes, in turn, may be mediated by systemic cytokinemia. [Copyright &y& Elsevier]

Background: Interleukin-18 (IL-18) production is the main mechanism of hepatic injury in several animal models via further gamma interferon (IFN-γ) release. IL-18 also functions as an inducer of proinflammatory cytokines as TNF-α, which are also shown to induce organ injuries in many severe inflammatory conditions. To clarify the mechanism of hepatic injury developed in acute pancreatitis, plasma concentrations of IL-18 and its related cytokines were analyzed. Patients and methods: Plasma levels of IL-18, IL-12, IFN-γ, TNF-α, soluble TNF receptor (sTNF-R) and soluble Fas ligand (sFas-L) were measured by ELISA. Results: Plasma concentrations of IL-18 in patients with hepatic injury increased during the first few days apparently and remained so to some extent thereafter. However, IFN-γ showed no apparent increase in plasma concentrations. Those of TNF-α and sTNF-R remained increased in the hepatic injury group. Conclusion: These results suggest that IL-18 may act as a pro-inflammatory cytokine, which provokes the cytokine storm and eventually hepatic injury. [Copyright &y& Elsevier]

Tumor necrosis factor-α (TNF-α) is known to play a central part in the pathogenesis of acute pancreatitis. TNF-α and its two receptors (p55 and p75 TNF receptors) have shown to be expressed at various sites in the body. TNF-α is initially expressed as a 26-kDa membrane-associated perform, which is proteolytically processed to a 17-kDa secreted mature form. Recently, TNF-α converting enzyme (TACE) has been identified as a membrane-bound TNF-α activating enzyme. Hence, it is expected that the newly devised TACE inhibitor, Y39083, will be a useful candidate for the treatment of inflammatory disorders provoked by TNF-α, including acute pancreatitis. Y39083 suppressed TNF-α production in vitro and in vivo significantly. However, the production of other cytokines, such as IL-1β, IFNγ and IL-6, in vivo were not. The blockade of secreted TNF-α production by Y39083 could not improve the organ injury.These results suggest that the blockade of activities of secreted TNF-α production is not sufficient to suppress systemic cytokine reaction and distant organ injury. [Copyright &y& Elsevier]