Alteration of peripheral blood lymphocyte subsets in acute pancreatitis

Pietruczuk, Mirosława; Dąbrowska, Milena; Wereszczyńska-Siemiątkowska, Urszula; Dâbrowski, A

doi:10.3748/wjg.v12.i33.5344

Cited by 67 publications

(78 citation statements)

References 31 publications

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“…Furthermore, the number of neutrophils increased in venous blood samples in both study groups. Circulating lymphocytes decreased in edematous and necrotic pancreatitis, a development that was also reported in a previous human study [32].…”

Section: Discussionsupporting

confidence: 86%

Acute edematous and necrotic pancreatitis in a porcine model

Meriläinen

Mäkelä

Anttila

et al. 2008

Scandinavian Journal of Gastroenterology

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Section: Discussionsupporting

confidence: 86%

Acute edematous and necrotic pancreatitis in a porcine model

Meriläinen

Mäkelä

Anttila

et al. 2008

Scandinavian Journal of Gastroenterology

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“…Serum and pancreatic levels of IL-12 and IL-18 are elevated in patients with AP and correlate with disease severity (20)(21)(22)(23)(24)(25). Elevation of IL-12 and IL-18 is likely responsible for the increased IFN-␥ serum levels and expression by CD8 ϩ lymphocytes infiltrating the pancreas in patients with severe AP (26)(27)(28). Furthermore, increased levels of IL-18 are observed in obese patients (29,30).…”

mentioning

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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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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“…However, apoptosis of CD4 lymphocytes was not related to the late resolution of SIRS. Lymphopenia arising in acute pancreatitis of either mild or moderate severity has also been described in other cohorts of patients [19,20]. …”

Section: Discussionmentioning

confidence: 85%