Influence of levamisole on pancreatic infection in acute pancreatitis

doi:10.1016/0002-9610(92)90260-X

The American Journal of Surgery

Volume 163, Issue 1, January 1992, Pages 100-104

https://doi.org/10.1016/0002-9610(92)90260-X Get rights and content

Abstract

We investigated the effect of levamisole on pancreatic infection in a model of acute pancreatitis (AP) in cats. Animals with and without AP received Escherichia coli intravenously. Blood was then taken at intervals for culture. AP reduced phagocytic function by 28% as measured by the rate of bacterial disappearance from the blood (p < 0.03). In other cats, AP was induced, and E. coli were placed into the pancreatic duct. Levamisole was given orally in some cats; the remainder were untreated. Control cats (neither AP nor levamisole) also received E. coli. Seven days later, pancreases from all control cats were sterile. In AP cats, the pancreatic infection rate was 73%. Levamisole reduced the rate of infection to 22% (p < 0.03). We concluded that phagocytic function was impaired in cats with AP. Levamisole reduced the rate of pancreatic infection.

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Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis
2003, Journal of Gastrointestinal Surgery
Intestinal barrier failure and subsequent bacterial translocation have been implicated in the development of organ dysfunction and septic complications associated with severe acute pancreatitis. Splanchnic hypoperfusion and ischemia/reperfusion injury have been postulated as a cause of increased intestinal permeability. The urinary concentration of intestinal fatty acid binding protein (IFABP) has been shown to be a sensitive marker of intestinal ischemia, with increased levels being associated with ischemia/reperfusion. The aim of the current study was to assess the relationship between excretion of IFABP in urine, gut mucosal barrier failure (intestinal hyperpermeability and systemic exposure to endotoxemia), and clinical severity. Patients with a clinical and biochemical diagnosis of acute pancreatitis were studied within 72 hours of onset of pain. Polyethylene glycol probes of 3350 kDa and 400 kDa were administered enterally, and the ratio of the percentage of retrieval of each probe after renal excretion was used as a measure of intestinal macromolecular permeability. Collected urine was also used to determine the IFABP concentration (IFABP-c) and total IFABP (IFABP-t) excreted over the 24-hour period, using an enzyme-linked immunosorbent assay technique. The systemic inflammatory response was estimated from peak 0 to 72-hour plasma C-reactive protein levels, and systemic exposure to endotoxins was measured using serum IgM endotoxin cytoplasmic antibody (EndoCAb) levels. The severity of the attack was assessed on the basis of the Atlanta criteria. Sixty-one patients with acute pancreatitis (severe in 19) and 12 healthy control subjects were studied. Compared to mild attacks, severe attacks were associated with significantly higher urinary IFABP-c (median 1092 pg/ml vs. 84 pg/ml; P < 0.001) and IFABP-t (median 1.14 μg vs. 0.21 μg; P = 0.003). Furthermore, the control group had significantly lower IFABP-c (median 37 pg/ml; P = 0.029) and IFABP-t (median 0.06 μg; P = 0.005) than patients with mild attacks. IFABP correlated positively with the polyethylene glycol 3350 percentage retrieval (r = 0.50; P < 0.001), CRP (r = 0.51; P < 0.001), and inversely with serum IgM EndoCAb levels (r = −0.32; P = 0.02). The results of this study support the hypothesis that splanchnic hypoperfusion contributes to the loss of intestinal mucosal integrity associated with a severe attack of pancreatitis. ( J Gastrointest Surg 2003;7:26–36.)
Pathogenesis of Infection in Pancreatic Inflammatory Disease
2001, Pancreatology
Bacterial Infection of Pancreatic Necrosis: Role of Bacterial Translocation, Impact of Antibiotic Treatment
2001, Pancreatology
Frequency and time course of pancreatic and extrapancreatic bacterial infection in experimental acute pancreatitis in rats
2000, Surgery
Background: Infectious complications in severe pancreatitis are the main factors determining clinical course and outcome. The taurocholate model for acute necrotizing pancreatitis was evaluated for frequency and time course of pancreatic and extrapancreatic bacterial infection. Methods: Sixty-five male Wistar rats were divided into 5 groups of 13 animals each. Specimens for bacteriologic examination were taken, and pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals were killed 8, 16, 24, or 32 hours thereafter, and bacteriologic examination was performed. A control group of animals with intraductal infusion of 0.9% saline solution were killed after 32 hours. Results: There was no significant pancreatic infection in the control group and in the 8-hour group (1 of 13 rats). Sixteen and 24 hours after induction of pancreatitis, infection and inflammation of the pancreas were found in 77% (10 of 13 rats), and after 32 hours pancreatic infection occurred in 69% (9 of 13 rats). Extrapancreatic bacterial infection after 16 hours occurred in the liver (62%), spleen (62%), and mesenteric lymph nodes (46%). Bacteria infecting the pancreas reflected the bacterial spectrum of the large bowel and terminal ileum before induction of pancreatitis (Escherichia coli [77%], Proteus [43%], Enterococcus [37%], and Staphylococcus [23%]). Conclusions: Pancreatic infection is an early and frequent finding in the taurocholate model of acute necrotizing pancreatitis. Infection occurs between 8 and 16 hours after induction of pancreatitis. The source of infecting bacteria seems to be the large bowel or the terminal ileum. We present a useful model of severe pancreatitis in which to study bacterial translocation, the further route of spread, and therapeutic approaches. (Surgery 2000;127:427-32.)
Antimicrobial prophylaxis in acute pancreatitis: Selective decontamination versus antibiotics
1999, Bailliere's Best Practice in Clinical Gastroenterology
The results of several controlled clinical trials, published during the last 5 years, provide evidence of a beneficial role for early antimicrobial prophylaxis in severe acute pancreatitis. Pancreatic infections, especially Gram-negative, which are of major importance with regard to morbidity and mortality, are gut-derived. Early enteral administration of antibiotics therefore seems the most logical measure to nip the danger in the bud. Intravenous antibiotics should adequately penetrate (peri)pancreatic tissues, i.e. necrotic tissues, and should be effective against the prevalent flora in infected necrotic tissues. However, the optimal route of administration is still a matter of debate. In contrast to one clinical trial using selective decontamination (SD) (i.e. enteral antibiotics combined with short systemic prophylaxis until SD is established), no clinical trial using intravenous antibiotics has been reported in which both pancreatic infections as well as mortality were reduced. Although the evidence supporting enteral administration, i.e. SD, is not unimpressive, further controlled clinical trials, in which the different ways of administration are compared, are warranted.
Intestinal Microcirculation and Gut Permeability in Acute Pancreatitis: Early Changes and Therapeutic Implications
1998, Journal of Gastrointestinal Surgery
Translocation of bacteria from the intestine causes local and systemic infection in severe acute pancreatitis. Increased intestinal permeability is considered a promoter of bacterial translocation. The mechanism leading to increased gut permeability may involve impaired intestinal capillary blood flow. The aim of this study was to evaluate and correlate early changes in capillary blood flow and permeability of the colon in acute rodent pancreatitis of graded severity. Edematous pancreatitis was induced by intravenous cerulein; necrotizing pancreatitis by intravenous cerulein and intraductal glycodeoxycholic acid. Six hours after induction of pancreatitis, the permeability of the ascending colon was assessed by the Ussing chamber technique; capillary perfusion of the pancreas and colon (mucosal and subserosal) was determined by intravital microscopy. In mild pancreatitis, pancreatic capillary perfusion remained unchanged (2.13 ± 0.06 vs. 1.98 ± 0.04 nl·min⁻¹·cap⁻¹ [control]; P = NS), whereas mucosal (1.59 ± 0.03 vs. 2.28 ± 0.03 nl·min⁻¹·cap⁻¹ [control]; P <0.01) and subserosal (2.47 ± 0.04 vs. 3.74 ± 0.05 nl·min⁻¹·cap⁻¹ [control]; P <0.01) colonic capillary blood flow was significantly reduced. Severe pancreatitis was associated with a marked reduction in both pancreatic (1.06 ± 0.03 vs. 1.98 ± 0.04 nl·min⁻¹·cap⁻¹ [control]; P <0.01) and colonic (mucosal: 0.59 ± 0.01 vs. 2.28 ± 0.03 nl·min⁻¹·cap⁻¹ [control], P <0.01; subserosal: 1.96 ± 0.05 vs. 3.74 ± 0.05 nl·min⁻¹·cap⁻¹ [control], P <0.01) capillary perfusion. Colon permeability tended to increase with the severity of the disease (control: 147 ± 19 nmol·hr⁻¹·cm⁻²; mild pancreatitis: 158 ± 23 nmol·hr⁻¹·cm⁻²; severe pancreatitis: 181 ± 33 nmol·hr⁻¹·cm⁻²; P = NS). Impairment of colonic capillary perfusion correlates with the severity of pancreatitis. A decrease in capillary blood flow in the colon, even in mild pancreatitis not associated with significant protease activation and acinar cell necrosis or impairment of pancreatic capillary perfusion, suggests that colonic microcirculation is especially susceptible to inflammatory injury. There was no significant change in intestinal permeability in the early stage of pancreatitis, suggesting a window of opportunity for therapeutic interventions to prevent the later-observed increase in gut permeability, which could result in improved intestinal microcirculation.

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^☆: Presented at the 32nd Annual Meeting of the Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 20–22, 1991.

¹: From the Department of Surgery, UCLA School of Medicine, and the Department of Surgery, Sepulveda Veterans Administration Medical Center, Los Angeles, California.

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The American Journal of Surgery

Abstract

References (26)

Impaired clearance of Escherichia coli bacteremia in early biliary obstruction

Am J Surg

A model of hemorrhagic pancreatitis in cats: the role of 16,16-dimethyl prostaglandin E₂

Gastroenterology

Relationship between the functional status of the reticuloendothelial system and the outcome of experimentally induced pancreatitis in young mice

Gastroenterology

Beneficial effect of enhanced macrophage function in the trauma patient

Ann Surg

Emerging concepts in the control of surgical infections

Surgery

A physiological basis for the development of opportunistic infections in man

Ann Surg

Reticuloendothelial defense: its relevance to cardiopulmonary function in septic surgical, trauma and burn patients

Contemp Surg

The elimination of trypsin-α₂-macroglobulin complexes from the blood circulation in pigs during acute pancreatitis and after massive intravenous trypsin infusion

Scand J Clin Lab Invest

Determining the effect of antibiotics on bacterial growth by optical and electrical methods

A quantitative study of the kinetics of blood clearance of P32-labelled E. coli and staphylococci by the RES

J Exp Med

Host mechanisms that act to remove bacteria from the blood stream

Bact Rev

The outcome of pancreatic colonization in acute necrotizing pancreatitis and the efficacy of cefotaxime treatment

Pancreas

Cited by (43)

Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis

Pathogenesis of Infection in Pancreatic Inflammatory Disease

Bacterial Infection of Pancreatic Necrosis: Role of Bacterial Translocation, Impact of Antibiotic Treatment

Frequency and time course of pancreatic and extrapancreatic bacterial infection in experimental acute pancreatitis in rats

Antimicrobial prophylaxis in acute pancreatitis: Selective decontamination versus antibiotics

Intestinal Microcirculation and Gut Permeability in Acute Pancreatitis: Early Changes and Therapeutic Implications

Influence of levamisole on pancreatic infection in acute pancreatitis☆

Abstract

Am J Surg

Gastroenterology

Gastroenterology

Beneficial effect of enhanced macrophage function in the trauma patient

Ann Surg

Emerging concepts in the control of surgical infections

Surgery

A physiological basis for the development of opportunistic infections in man

Ann Surg

Reticuloendothelial defense: its relevance to cardiopulmonary function in septic surgical, trauma and burn patients

Contemp Surg

The elimination of trypsin-α2-macroglobulin complexes from the blood circulation in pigs during acute pancreatitis and after massive intravenous trypsin infusion

Scand J Clin Lab Invest

Determining the effect of antibiotics on bacterial growth by optical and electrical methods

A quantitative study of the kinetics of blood clearance of P32-labelled E. coli and staphylococci by the RES

J Exp Med

Host mechanisms that act to remove bacteria from the blood stream

Bact Rev

The outcome of pancreatic colonization in acute necrotizing pancreatitis and the efficacy of cefotaxime treatment

Pancreas

The elimination of trypsin-α₂-macroglobulin complexes from the blood circulation in pigs during acute pancreatitis and after massive intravenous trypsin infusion