Laboratory Markers of Severe Acute Pancreatitis

Rau, Bettina; Schilling, Martin K.; Beger, H. G.

doi:10.1159/000082796

Cited by 66 publications

(27 citation statements)

References 151 publications

(110 reference statements)

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“…However, only in ob/ob mice did levels fall below the critical level of 7 mg/dl. (34,36). Serum IL-6 was markedly elevated in ob/ob mice receiving IL-12 plus IL-18, whereas only a small and transient increase was observed in WT mice (Fig.…”

Section: Resultsmentioning

confidence: 90%

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Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice

Sennello¹,

Fayad²,

Pini³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Obesity is associated with increased severity of acute pancreatitis (AP). The cytokines IL-18 and IL-12 are elevated in patients with AP, and IL-18 levels are high in obesity. We aimed to develop a pathologically relevant model to study obesity-associated severe AP. Lean WT and obese leptin-deficient ob/ob mice received two injections of IL-12 plus IL-18. Survival, pancreatic inflammation, and biochemical markers of AP were measured. Dosing with IL-12 plus IL-18 induced 100% lethality in ob/ob mice; no lethality was observed in WT mice. Disruption of pancreatic exocrine tissue and acinar cell death as well as serum amylase and lipase levels were significantly higher in ob/ob than in WT mice. Edematous AP developed in WT mice, whereas obese ob/ob mice developed necrotizing AP. Adipose tissue necrosis and saponification were present in cytokine-injected ob/ob but not in WT mice. Severe hypocalcemia and elevated acute-phase response developed in ob/ob mice. The cytokine combination induced high levels of regenerating protein 1 and pancreatitis-associated protein expression in the pancreas of WT but not of ob/ob mice. To differentiate the contribution of obesity to that of leptin deficiency, mice received short-and long-term leptin replacement therapy. Shortterm leptin reconstitution in the absence of major weight loss did not protect ob/ob mice, whereas leptin deficiency in the absence of obesity resulted in a significant reduction in the severity of the pancreatitis. In conclusion, we developed a pathologically relevant model of AP in which obesity per se is associated with increased severity.cytokines ͉ inflammation ͉ obesity ͉ pancreas A cute pancreatitis (AP) is an inflammatory disorder that ranges from interstitial edema to confluent necrosis and hemorrhage. In severe cases, progress to circulatory shock, acute lung injury, renal failure, and eventual death may occur (1). Despite some controversy, numerous studies have demonstrated that obesity is associated with increased risk of the severe form of AP and with development of life-threatening complications (2-8). However, the mechanism by which increased adiposity worsens AP remains unknown.Leptin, a protein mainly produced by adipocytes, is a critical regulator of appetite (9). Leptin exerts important regulatory effects on inflammation (10). In the context of AP, the role of leptin remains controversial. In patients with AP, a correlation between serum leptin and disease severity has been reported by some investigators but not by others (11,12). Although in animal models administration of leptin decreases AP severity (13-16), more severe disease is present in leptin-deficient ob/ob and leptin receptordeficient db/db mice as well as leptin-receptor mutant fa/fa rats (17, 18). However, the differential effect of obesity versus leptin deficiency has not been fully investigated.IL-12 and IL-18 are two proinflammatory cytokines that drive the Th1 cell response, characterized by high levels of IFN-␥ (19). Both cytokines are mainly produced by monocytes/macrophages....

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Section: Resultsmentioning

confidence: 90%

“…Furthermore, ob/ob mice had a highly increased acute-phase response, which is associated with a more severe outcome in patients with AP (34,36). Another feature of severe AP in ob/ob mice, which is typically observed in obese AP patients, was the massive necrosis and saponification of adipose tissue, particularly in the retropancreatic area.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice

Sennello¹,

Fayad²,

Pini³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Having excluded this trial, we have constrained ourselves to the trials of nasojejunal EN v. central PN and reached a statistical homogeneity (as evidenced by Galbraith's radial plot and Q statistic). Finally, limitations of the scoring systems used to predict severity of acute pancreatitis are well known (52,53) and therefore some of the patients in the present systematic review may indeed have had a mild or moderate course of disease. Future clinical studies in acute pancreatitis have to be based on actual rather than predicted severity (54) .…”

Section: Discussionmentioning

confidence: 99%

Comparison of complications attributable to enteral and parenteral nutrition in predicted severe acute pancreatitis: a systematic review and meta-analysis

Petrov

Whelan

2010

Br J Nutr

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Enteral nutrition (EN) reduces infectious complications and mortality compared with parenteral nutrition (PN) in patients with predicted severe acute pancreatitis. However, to date the complications attributable to the administration of EN and PN in this patient group have not been comprehensively studied. The aim of the study was to systematically review the complications related to the use of nutrition in patients with predicted severe acute pancreatitis receiving EN v. PN. The Cochrane Library, MEDLINE and Scopus were searched. Randomised controlled trials (RCT) of EN v. PN in predicted severe acute pancreatitis were selected. Pooled estimates of complications were expressed as OR with corresponding 95 % CI. Data from five RCT were meta-analysed. Diarrhoea occurred in six of ninety-two (7 %) patients receiving PN and twenty-four of eighty-two (29 %) patients receiving EN (OR 0·20; 95 % CI 0·09, 0·43; P,0·001). Hyperglycaemia developed in twenty-one of ninety-two (23 %) patients receiving PN and nine of eighty-two (11 %) receiving EN (OR 2·59; 95 % CI 1·13, 5·94; P¼ 0·03). Given a significant reduction in infectious complications and mortality associated with the use of EN over PN that has been consistently demonstrated in previous studies, the former should be the treatment of choice in acute pancreatitis. Further clinical studies should investigate the strategies to mitigate the complications of enteral tube feeding in patients with acute pancreatitis.

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“…In the second phase, there is intrapancreatic inflammation through a variety of mechanisms and pathways (16,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). In the third phase, there is extrapancreatic inflammation including acute respiratory syndrome (ARDS) (16,(19)(20)(21)29).…”

Section: Pathophysiologymentioning

confidence: 99%