Effects of Immunosuppressive and Immunostimulative Treatment on Pancreatic Injury and Mortality in Severe Acute Experimental Pancreatitis

Rau, Bettina; Krüger, Colin M.; Hasel, Cornelia; Oliveira, Vilma; Rubie, Claudia; Beger, H. G.; Schilling, Martin K.

doi:10.1097/01.mpa.0000226895.16817.a1

Cited by 31 publications

(20 citation statements)

References 44 publications

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“…In our study, we also demonstrated that the level of IL-1b, which was one of the most powerful proinflammatory cytokines, together with TNF-a determining the increase in overall mortality, the distant organ complications [9] were significantly suppressed. Various studies have shown that levels of IL-1b are increased in the model of acute pancreatitis [11,12]. A similar outcome was obtained with pancreatitisinduced vehicle treated rats in our study.…”

Section: Discussionsupporting

confidence: 93%

“…Tumor necrosis factor-a (TNF-a), IL1b, IL-6, IL-8, platelet activation factor, and the chemokines are produced as the major pro-inflammatory mediators whose serum concentrations correlate with mortality of the acute pancreatitis [6][7][8]. Thus, in order to lower the pancreatic damage and mortality, various approaches to attenuate the pro-inflammatory immune response and anti-inflammatory therapy modalities have been proposed [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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The Selective Inhibition of Type IV Phosphodiesterase Attenuates the Severity of the Acute Pancreatitis in Rats

et al. 2009

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Phosphodiesterases (PDEs) are enzymes primarily responsible for regulation of the intracellular cyclic nucleotides. Among these enzymes, the type 4 PDE is highly expressed in most immune and inflammatory cells and its inhibition causes the suppression of immune and inflammatory cell activity, including production of cytokines. This study was designed to investigate the efficacy of the type 4 PDE inhibitor rolipram on acute pancreatitis in rats. Rats were divided into three groups--treatment, control, and sham. In the treatment and control groups, rats were pretreated with rolipram and vehicle before acute pancreatitis was induced. The pretreatment of rats with rolipram significantly reduced the amylase (P<0.0001) and IL-1β levels (P=0.002) compared to vehicle treated rats. Also, mean histopathological scores were significantly reduced by rolipram treatment (P<0.005). It can be concluded that rolipram ameliorates severity of pancreatitis in rats.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

The Selective Inhibition of Type IV Phosphodiesterase Attenuates the Severity of the Acute Pancreatitis in Rats

et al. 2009

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“…Ohmoto and Yamamoto [26] found that, the ratio of serum IL-10 and IL-6 significantly decreased in SAP patients before treatment, the ratio increased back after treatment. In the late stage of this disease, the levels of IL-10, IL-4, IL-6, and TNF-α decline, but the relative levels of IL-10, IL-4 are higher, which are potential factors contributing to the infection present in the late stage of SAP [27,28]. After experiencing the processes of an emergency situation, we found that the levels of pro-inflammatory cytokines TNF-α, IL-6 declined in minimum, and antiinflammatory cytokines IL-10 and IL-4 peaked on days 14 in the infection and the MODS group.…”

Section: Discussionmentioning

confidence: 95%

Immune Dysregulation in Patients with Severe Acute Pancreatitis

et al. 2010

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To investigate patients with severe acute pancreatitis (SAP) by dynamic levels of pro-/anti-inflammatory cytokines and endotoxin (ET) in plasma and the relationship between immunity and infection, organ dysfunction. Seventy-two patients with SAP were recruited. The ET, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-4 (IL-4) were determined on admission and days 3, 7, and 14. For comparison, patients were analyzed through infection group versus non-infection group, multiple organ dysfunction syndrome (MODS) group versus non-MODS group. There were sixteen patients with secondary infection, twenty-two with MODS, and nine deaths. The infection group had higher levels of ET than the non-infection group on days 3 and 7. The dynamic cytokine levels of patients in the MODS group were unanimous with those outcomes in the infection group. The levels of cytokines in the infection group were different from the non-infection group, with more levels of TNF-α, IL-6 on days 3 and 7 and less on days 14, and more levels of IL-10, IL-4 on days 7 and 14. The levels of TNF-α, IL-6 in the MODS group were different from the non-MODS group, with more levels on days 3 and 7, and less levels on days 14. Immune dysregulation may play an important role in infection and organ dysfunction for patients with SAP.

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“…Indeed, it has been reported from a number of clinical studies that the low expression of HLA-DR is related to the excessive inflammatory response [14,15]. The low level of HLA-DR expression was found in SAP patients on admission, suggesting immune suppression emerged very early in the course of the disease.…”

Section: Discussionmentioning

confidence: 97%

Fish Oil-Supplemented Parenteral Nutrition in Severe Acute Pancreatitis Patients and Effects on Immune Function and Infectious Risk: A Randomized Controlled Trial

Wang

Zhang

et al. 2009

Inflammation

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The human leukocyte antigen (HLA)-DR expression on monocytes and plasma Interleukin (IL)-10 levels are key indicators of immune response during the acute phase of severe acute pancreatitis (SAP). We designed a pilot study to investigate whether omega-3 fatty acids (FAs) supplemented parenteral nutrition (PN) could improve immune response in SAP patients. Fifty-six SAP patients were enrolled (28 patients in each group) and received isocaloric and isonitrogenous parenteral nutrition, providing 1.0 g/kg/day standard soybean-oil based fat (omega-6 FAs group) or 0.8 g/kg/day soybean oil +0.2 g/kg/day omega-3 FAs based fat (omega-3 FAs group). IL-10, HLA-DR and the ratio of CD4(+) to CD8(+) were determined before PN treatment and on day 6 after starting PN. The infection and surgery rates were recorded until hospital discharge. A significant IL-10 increase was associated with the administration of omega-3 FAs (p = 0.04, vs omega-6 FAs group). Monocyte HLA-DR expression improved in both groups after 5 days of PN treatment. This increase was significantly higher in the omega-3 FAs group compared to omega-6 FAs (p = 0.01). There was no significant difference of CD4(+)/CD8(+), infection and surgery rates between the two groups. In conclusion, omega-3 FAs supplemented PN can elevate the IL-10 level and HLA-DR expression in SAP patients. A larger trial is required to see whether omega-3 FAs supplemented PN treatment in SAP patients would result in better clinical outcomes than omega-6 FAs.

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Effects of Immunosuppressive and Immunostimulative Treatment on Pancreatic Injury and Mortality in Severe Acute Experimental Pancreatitis

Cited by 31 publications

References 44 publications

The Selective Inhibition of Type IV Phosphodiesterase Attenuates the Severity of the Acute Pancreatitis in Rats

The Selective Inhibition of Type IV Phosphodiesterase Attenuates the Severity of the Acute Pancreatitis in Rats

Immune Dysregulation in Patients with Severe Acute Pancreatitis

Fish Oil-Supplemented Parenteral Nutrition in Severe Acute Pancreatitis Patients and Effects on Immune Function and Infectious Risk: A Randomized Controlled Trial

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