Caerulein-induced Acute Pancreatitis In Rats Research Articles

Visualization, Quantification and Characterization of Caerulein-Induced Acute Pancreatitis in Rats by 3.0T Clinical MRI, Biochemistry and Histomorphology.

Purpose: To investigate whether Caerulein-induced acute pancreatitis (AP) in rats could be noninvasively studied by clinical magnetic resonance imaging (MRI) techniques and validated by enzymatic biochemistry and histomorphology.Materials and Methods: The study was approved by the institutional animal ethical committee. The AP was induced in 26 rats by intraperitoneal injections of Caerulein, as compared to 6 normal rats. T2-weighted 3D MRI, T2 relaxation measurement and contrast enhanced T1-weighted MRI were performed at 3 Tesla. Pancreatic volume and contrast ratio of pancreas against surrounding tissues were measured by MRI. Animals were scarified at 3, 8, 24 and 48-hr respectively for analyses of serum lipase and amylase levels, and biliopancreatic perfusion-assisted histomorphology.Results: The AP could be observed on MRI 3-hr onwards after Caerulein-administration. T2 relaxation within the pancreas was prolonged due to high water content or edema. Increase of vascular permeability was indicated by T1 contrast enhancement. Both edema and vascular permeability gradually recovered afterwards (p<0.05/0.01), paralleled by declining serum enzyme levels (p<0.05). Microscopy revealed cell vacuolization and edema for early stage, and increased inflammatory cell infiltration and acinar cell loss after 24 and 48-hr.Conclusion: Multiparametric MRI techniques at 3.0T could facilitate noninvasive diagnosis and characterization of Caerulein induced AP in rats, as validated by a novel ex vivo method.

Promoting effect of adipocytokine, apelin, on hepatic injury in caerulein-induced acute pancreatitis in rats: Apelin on AP-induced hepatic injury

ObjectiveTo evaluate the potential apelin effect on hepatic injury in caerulein (Cn) -induced AP in rats. Experimental protocolThirty male albino rats were divided into three groups, 10 rats each: control group: received 0.9% NaCl solution. AP group: received (Cn, 50μg/kg/h, i.p.) for 6h. Apelin-13 treated AP group: received apelin 13, 50nmol/kg/h, i.p, immediately after each Cn injection, starting after the second Cn dose. 12h after the last Cn injection, the rats were sacrificed, and serum amylase, lipase, phospholipase A2 (PLA2), interleukin (IL)-6, IL-1β, IL-10, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactic dehydrogenase activity (LDH) were assayed. The hepatic malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT) levels, caspase-3 activity and tumor necrosis factor-alpha (TNF-α) were assessed, while myeloperoxidase (MPO) was determined in pancreatic and hepatic tissues. ResultsCn injection caused severe AP, with marked hepatic damage. The exogenous apelin reduced Cn-induced pancreatic and hepatic injury with reduction in hepatic oxidative, apoptotic and inflammatory markers, pancreatic and hepatic MPO activity with modulation of inflammatory cytokines. ConclusionApelin could be protective in AP associated liver damage, possibly through anti-oxidant, anti-apoptotic mechanisms with modulating the inflammatory mediators.

Effects of GamiChungYi-tang on the Caerulein-induced Acute Pancreatitis in Rats

In this study, we aimed to investigate the effect of GamiChungYi-tang(GCY-t) on caerulein-induced acute pancreatitis (AP). It is performed by detecting oxidative stress markers and observing histopathological examination. Thirty adult male rats(Sprague-Dawley) were divided into six groups as follows: normal (NOR,n=5), caerulein-induced (CON,n=5), caerulein+Cefotaxime Sodium(CT,n=5), caerulein+GCY-t (130 ㎎/㎏, CHA,n=5), caerulein+GCY-t (260 ㎎/㎏, CHB,n=5) and caerulein+GCY-t (520 ㎎/㎏, CHC,n=5) groups. Pancreatic tissues of rats from all groups were removed for apoptosis and light, and electron microscopic examination. Blood of rats from all groups were collected for oxidative stress markers inspection and pathological examination. Pancreatic oxidative stress markers were evaluated by the measurements of leukocyte, serum amylase and platelet activating factor (PAF), Interleukin-6 (IL-6) levels were determined spectrophotometrically. CON group has a significant increase (p<0.05) in amylase compared with NOR, but CT and CHA, CHB, CHC groups reduced the levels of these enzyme. The levels of Platelet activating factor (PAF) were increased in CON compared with NOR, but decreased in CT and CHA, CHB, CHC groups compared with CON. Interleukin-6 (IL-6) levels were increased significantly in CON compared with NOR, but reduced in CT and CHA, CHB, CHC groups. In the observations of Optical microscopy and electron microscopy, The experimental groups showed the significant decreases in pancreatic tissue inflammation, edema, vacuolization, necrosis compared to the control group. After all, GCY-t is potentially capable of limiting pancreatic damage produced during AP by restoring the fine structure of acinar cells and tissue.

Protective Effects of Sivelestat in a Caerulein-Induced Rat Acute Pancreatitis Model

In the present study, we investigated the protective effects of sivelestat on acute pancreatitis (AP) in a rat model. Sivelestat is a specific neutrophil elastase inhibitor, which has been developed in Japan in 1991. Varying doses of sivelestat in normal saline were infused continuously in sivelestat-treated groups through osmotic pumps. Blood and pancreas samples were collected for serological and histopathological studies, and ten rats in each group were taken for survival observation. Increasing doses of sivelestat inhibits the expression of lipase, amylase, corticosterone, IL-1β, TNF-α, and nuclear factor-κB. Furthermore, sivelestat reduces the inflammatory cells infiltration, histological damage, and mortality rate. Meanwhile, the total antioxidant power and serum level of IL-4 in high-dose sivelestat-treated groups were increased. Our findings suggest that the increasing doses of sivelestat protect against caerulein-induced AP in rats, and this protection is possibly associated with the anti-inflammatory ability of sivelestat.

The effect of Flos lonicerae on caerulein-induced pancreatitis in rats

Acute pancreatitis (AP) is associated with significant morbidity and mortality; however, there is no specific treatment for this disease. Our objective is to study how Flos Lonicerae, an herbal medicine used for treating inflammation within oriental medicine practices, affects inflammation and acinar cell injury during the early phase of AP. A total of twenty-four male Sprague-Dawley rats were randomly allocated into a normal group, a control group, and two AP with F. lonicerae extract groups. A single dose of F. lonicerae water extract (100 or 200 mg/kg) was co-administered with caerulein 2 h before AP induction. Plasma amylase activities, the concentration of platelet activating factor (PAF), tumor necrosis factor (TNF-α), and interleukin 6 (IL-6) were measured. Pancreatic sections were histological and COX-2 immunohistologically assessed for abnormal acinar cells and interstitial space. AP induction produced a sevenfold increase in plasma amylase and a threefold increase in interstitial space. Observations also showed that 90% of the acinar cells were abnormal. For rats from the AP F. lonicerae extract groups, serum amylase and IL-6 were reduced by 86 and 84% relative to the control group (p < 0.05) at 6 h, respectively. Histological severity of pancreatitis, graded on the basis of pancreatic edema, acinar cell vacuolization and inflammation, was reduced in the F. lonicerae extract administered rats. These results suggest that F. lonicerae water extract has an ameliorative effect for suppressing inflammation on caerulein-induced AP in rat. Key words: Flos Lonicerae, pancreatitis, immunohistochemistry.

Acetyl-l-Carnitine Ameliorates Caerulein-induced Acute Pancreatitis in Rats

In the present study, we have addressed the possible protective role of acetyl-L-carnitine in caerulein-induced acute pancreatitis in male Swiss albino rats. Acute pancreatitis paradigm was developed by challenging animals with a supramaximal dose of caerulein (20 microg/kg, SC) four times at hourly intervals. Caerulein induced acute pancreatitis that was well-characterized morphologically and biochemically. Severe oedema with marked increased relative pancreatic weight, marked atrophy of acini with increased interacinar spaces, vacuolization, and extensive leucocytic infiltration were diagnostic fingerprints of the pancreatitis phenotype. A biochemical test battery that confirmed the model comprised increased plasma amylase and lipase activities, calcium levels as well as increased pancreatic enzymatic myeloperoxidase and glutathione-S-transferase activities, beside increased pancreatic contents of nitric oxide and malondialdehyde and reduced pancreatic glutathione level. Prior administration of acetyl-L-carnitine (200 mg/kg, IP) for seven consecutive days ahead of caerulein challenge alleviated all the histological and biochemical manifestations of acute pancreatitis. These results suggest a possible protective role of the carnitine ester in such a murine acute pancreatitis model probably via regulation of the oxidant/antioxidant balance, beside modulation of the myeloperoxidase and nitric oxide systems, which are involved in the inflammatory cascade that most often associate the disease.

The Beneficial Effects of Pentoxifylline on Caerulein-Induced Acute Pancreatitis in Rats

In this study we aimed to investigate the effect of pentoxifylline on caerulein-induced acute pancreatitis (AP) by detecting oxidative stress markers and performing histopathological examination. Twenty-one adult female Sprague-Dawley rats were divided into three groups as follows: control, caerulein, and caerulein + pentoxifylline groups. Pancreatic tissues of rats from all groups were removed for light and electron microscopic examination and determination of oxidative stress markers. Pancreatic oxidative stress markers were evaluated by the measurements of malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and total glutathione (GSH). Serum amylase and lipase levels were determined spectrophotometrically. The pancreatic damage score was significantly increased (P < 0.005) in the caerulein group, whereas it was decreased (P < 0.05) in the caerulein+ with pentoxifylline group. MDA levels, CAT, SOD, GPx, and GSH activities were significantly altered (P < 0.05, P < 0.005) in the caerulein group and indicated increased oxidative stress. Oxidative stress markers were normalized with pentoxifylline administration. Caerulein administration resulted in significant increase (P < 0.05) in amylase and lipase levels; pentoxifylline reduced the levels of these enzymes. Pentoxifylline is potentially capable of limiting pancreatic damage produced during AP by restoring the fine structure of acinar cells and tissue antioxidant enzyme activities. We concluded that pentoxifylline may have beneficial effects in the treatment of caerulein-induced AP.

The contradictory effects of nitric oxide in caerulein-induced acute pancreatitis in rats

This study was planned to observe the effects of nitric oxide synthesis on the antioxidative defense enzymes and pancreatic tissue histology in caerulein-induced acute pancreatitis. Acute pancreatitis was induced by intraperitoneal injections of 50 µg/kg caerulein, L-arginine used for NO induction and Nω-nitro-L-arginine methyl ester (L-NAME) used for NO inhibition. In the caerulein group acinar cell degeneration, interstitial inflammation, oedema and haemorrhage were detected. Pancreatic damage scores were decreased with both NO induction and inhibition (p<0.05). MDA, GSH-Px, CAT, GSH and SOD activities were significantly changed in the caerulein group and indicated increased oxidative stress. Both NO induction and inhibition decreased this oxidative stress. It is concluded that both nitric oxide induction and inhibition ameliorated caerulein-induced acute pancreatitis. The findings indicate that a certain amount of NO production has beneficial effects in experimental acute pancreatitis, but uncontrolled over-production of NO may be detrimental.

Acute Pancreatitis: Bench to the Bedside

Acute Pancreatitis: Bench to the Bedside

Effect of endothelin-1 receptor antagonists on histological and ultrastructural changes in the pancreas and trypsinogen activation in the early course of caerulein-induced acute pancreatitis in rats

To assess the effect of non-selective ET(A/B) (LU 302872) and selective ET(A) (LU 302146) antagonist on pancreatic histology and ultrastructure of acinar cells in connection with trypsinogen activation in early caerulein-induced AP. Male Wistar rats with caerulein-induced AP, lasting 4 h, were treated i.p. with 10 and 20 mg/kg b.w. of each antagonist. Edema, inflammatory infiltration, necrosis and vacuolization of acinar cells in the pancreas were scored at 0-3 scale. Free active trypsin (FAT), total potential trypsin (TPT) after activation with enterokinase, and index of trypsinogen activation (%FAT/TPT) were assayed in pancreatic homogenates. In untreated AP, the edema, inflammatory infiltration, necrosis and vacuolization increased as compared to control healthy rats (P<0.01). None of the treatment exerted any meaningful effect on the edema and inflammatory infiltration. The selective antagonist increased slightly the necrosis score to 0.82+/-0.06 at higher dose (P<0.05) vs 0.58+/-0.06 in untreated AP. The non-selective antagonist increased slightly the vacuolization score to 2.41+/-0.07 at higher dose (P<0.01) vs 1.88+/-0.08 in untreated AP. The decrease in the number of zymogen granules, disorganization of endoplasmic reticulum, autophagosomes and cytoplasmic vacuoles were more prominent in treated AP than in untreated AP groups. %FAT/TPT in untreated AP increased about four times (18.4+/-3.8 vs 4.8+/-1.3 in control group without AP, P<0.001). Treatment of AP with both antagonists did not affect significantly augmented trypsinogen activation. The treatment with endothelin-1 receptors (non-selective ET(A/B) and selective ET(A)) antagonists has essential effect neither on the edema and inflammatory infiltration nor on trypsinogen activation observed in the early course of caerulein-induced AP. Nevertheless a slight increase of the necrosis and vacuolization score and some of the ultrastructural data could suggest the possibility of their undesired effects in caerulein-induced AP at investigated doses.

Heparin improves organ microcirculatory disturbances in caerulein-induced acute pancreatitis in rats.

Microcirculatory disturbances are important early pathophysiological events in various organs during acute pancreatitis. The aim of the study was to evaluate changes in microperfusion of the pancreas, liver, kidney, stomach, colon, skeletal muscle, and to investigate the influence of heparin on the organ microcirculation in caerulein-induced experimental acute pancreatitis. Acute pancreatitis was induced by 4 intraperitoneal injections of caerulein (Cn) (15 microg/kg). The organ microcirculation was measured by laser Doppler flowmetry. Serum interleukin 6 and hematocrit levels were analysed. Acute pancreatitis resulted in a significant drop of microperfusion in all examined organs. Heparin administration (2 x 2.5 mg/kg) improved the microcirculation in pancreas (36.9 +/- 4% vs 75.9 +/- 10%), liver (56.6 +/- 6% vs 75.2 +/- 16%), kidney (45.1 +/- 6% vs 79.3 +/- 5%), stomach (65.2 +/- 8% vs 78.1 +/- 19%), colon (69.8 +/- 6% vs 102.5 +/- 19%), and skeletal muscle (59.2 +/- 6% vs 77.9 +/- 13%). Heparin treatment lowered IL-6 (359.0 +/- 66 U/mL vs 288.5 +/- 58 U/mL) and hematocrit level (53 +/- 4% vs 46 +/- 3%). Heparin administration has a positive influence on organ microcirculatory disturbances accompanying experimental Cn-induced acute pancreatitis.

Pancreatic gene expression during the initiation of acute pancreatitis: identification of EGR-1 as a key regulator.

We hypothesized that genes expressed in pancreatic acinar cells during the initiation of acute pancreatitis determine the severity of the disease. Therefore, we utilized microarrays to identify those genes commonly induced in rat pancreatic acinar cells within 1-4 h in two in vivo models, caerulein and taurocholate administration. This strategy yielded 51 known genes representing a complex array of molecules, including those that are likely to either reduce or increase the severity of the disease. Novel genes identified in the current study included ATF3, BRF1, C/EBPbeta, CGRP, EGR-1, ephrinA1, villin2, ferredoxin, latexin, lipocalin, MKP-1, NGFI-B, RhoA, tissue factor (TF), and syndecan. To validate these microarray results, the role of EGR-1 was further investigated using quantitative RT-PCR, Western blotting, and immunocytochemistry. EGR-1 expression occurred within acinar cells and correlated with the development of caerulein-induced acute pancreatitis in rats. Furthermore, the levels of the inflammation-related genes MCP-1, PAI, TF, IL-6, and ICAM-1 and the extent of lung inflammation were reduced during the initiation of caerulein-induced acute pancreatitis in EGR-1-deficient mice. Thus this study identified EGR-1 and several other novel genes likely to be important in the development and severity of acute pancreatitis.

Nitric Oxide Regulates Bacterial Translocation in Experimental Acute Edematous Pancreatitis

Background/Aims: The role of nitric oxide (NO) in bacterial translocation (BT) associated with acute pancreatitis is controversial. We investigated the effects of the NO synthase substrate, L-arginine, and the NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on BT in caerulein-induced acute pancreatitis in rats. Methods: Acute pancreatitis was induced by subcutaneous injections of caerulein (12 µg/kg) at 6-hour intervals for 2 days. Subcutaneous injections of L-arginine (100 mg/kg) or L-NAME (10 mg/kg) were administeredonce daily for 2 days. At 48 h, pancreatic injury and BT to the mesenteric lymph nodes (MLN), liver, and peritoneum were assessed. Results: Compared with controls, rats that received caerulein injections alone had increased BT to the MLN and pancreatic inflammatory changes. L-Arginine significantly reduced the inflammation and BT caused by caerulein. L-NAME did not significantly alter pancreatic inflammation. Although caerulein + L-NAME-treated rats had increased BT to the peritoneum, MLN, and liver compared with controls, rates of BT did not significantly differ between caerulein alone- and caerulein + L-NAME-treated rats. Conclusion: In acute edematous pancreatitis, BT is increased and is regulated by NO. NO substrates limit BT and pancreatic inflammation associated with acute pancreatitis, probably by their bactericidal actions and ability to improve pancreatic blood flow.

Alteration of myofibroblast localization, basic fibroblast growth factor and platelet-derived growth factor immunoreactivity in onset and resoration process of caerulein-induced acute pancreatitis in rat

Alteration of myofibroblast localization, basic fibroblast growth factor and platelet-derived growth factor immunoreactivity in onset and resoration process of caerulein-induced acute pancreatitis in rat

Protective effects of prostaglandin E1 on acute lung injury of caerulein-induced acute pancreatitis in rats.

Infusion of a supramaximally stimulating dose of the pancreatic secretagogue caerulein (10 micrograms.kg-1.h-1) for 4 h induces interstitial edematous acute pancreatitis in rats. This model of acute pancreatitis is associated with evidence of acute lung injury, including sequestered neutrophils within the pulmonary microvasculature, increased microvascular permeability, and interstitial pulmonary edema. Infusion of prostaglandin E1 (PGE1; 50 ng.kg-1.min-1) along with caerulein does not alter the severity of secretagogue-induced pancreatitis, but it does reduce the severity of pancreatitis-associated acute lung injury. The rise in lung weight, lung water content, and pulmonary microvascular permeability and the sequestration of neutrophils within the pulmonary microvasculature that accompany secretagogue-induced pancreatitis are all reduced by infusion of PGE1. Infusion of PGE1 does not interfere with polymorphonuclear neutrophil sequestration in the pancreas or reduce the enhanced expression of CD11b/c receptors on circulating neutrophils. Our observations indicate that PGE1 reduces the severity of pancreatitis-associated acute lung injury by preventing neutrophil sequestration within the lung. We speculate that PGE1 interferes with neutrophil sequestration by dilating pulmonary vasculature, increasing pulmonary flow rate, and reducing neutrophil-endothelial cell interaction and attachment.

Effects of nafamostat mesilate, somatostatin, and glucagon on caerulein-induced acute pancreatitis in rats

The inhibitory effects of somatostatin (SMS) and glucagon (Gn) on acute pancreatitis were evaluated in an experimental acute pancreatitis model in male Wistar rats. The effects of these agents were compared with those of nafamostat mesilate (NM). The acute pancreatitis was induced by four serial subcutaneous injections of caerulein. The rats were divided into four groups. The first group (n=28) received SMS daily, the second group (n=28) received Gn daily, and the third group (n=28) received NM daily after the first injection of caerulein. The fourth group (n=42) received caerulein alone and served as the control group. Animals were sacrificed 4, 6, 8, 12, and 24 h, and 3 and 7 days after the first administration of caerulein and the degree of severity of the acute pancreatitis was evaluated by serial morphological and histological examinations of pancreatic tissues, as well as in terms of the serum concentrations of amylase and lipase. The characteristic findings of acute pancreatitis in the animals of all groups treated with SMS, Gn, or NM were markedly attenuated at all time points after the treatments compared with findings in the controls (caerulein alone) in terms of wet weight of pancreas, serum concentrations of amylase and lipase, formation of intracellular vacuoles in acinar cells, interstitial edema, and infiltration of an inflammatory cell component. The inhibitory effects of SMS, Gn, and NM on acute pancreatitis were similar at the doses used. These results suggest that SMS and Gn are as useful as NM, they may be of value for the treatment of acute pancreatitis.

Inhibition of gut motility acceleretes bacterial translocation and incidence of endotoxemia in caerulein-induced acute pancreatitis in rat

Inhibition of gut motility acceleretes bacterial translocation and incidence of endotoxemia in caerulein-induced acute pancreatitis in rat

Nitric oxide in pancreatic secretion and hormone-induced pancreatitis in rats

The aim of the present study was to determine the role of endogenous nitric oxide (NO) in pancreatic secretion in vivo and amylase release from pancreatic acini in vitro and in caerulein-induced acute pancreatitis in rats. Blockade of NO synthase by NG-nitro-L-arginine (L-NNA) (2.5 mg/kg i.v.) significantly reduced basal pancreatic protein secretion and that induced by the infusion of CCK (0.5 micrograms/kg-h), feeding, and the diversion of pancreatic juice in rats with pancreatic fistula. This inhibitory effect was partially reversed when L-arginine (50 mg/kg-h i.v.) was added to L-NNA. L-Arginine alone (50 mg/kg i.v.) did not affect basal or caerulein-induced pancreatic secretion. L-NNA, L-arginine, or their combination added in various concentrations to the incubation medium of dispersed acini failed to affect basal or secretagogue (caerulein or urecholine) stimulated amylase release. Infusion of caerulein (5 micrograms/kg-h) for 5 h produced histological changes of acute edematous pancreatitis accompanied by a marked increase in pancreatic protein content and about 50% reduction in tissue blood flow. L-NNA alone also reduced the pancreatic blood flow and caused a significant increase in pancreatic weight and protein content. L-NNA significantly potentiated the inflammatory changes in the pancreas caused by caerulein. Addition of L-arginine enhanced the pancreatic blood flow and ameliorated the pancreatitis induced by caerulein alone or that combined with L-NNA. We conclude that NO is involved in the stimulation of pancreatic secretion in vivo and exhibits a beneficial effect on pancreatitis, probably by improving the pancreatic blood flow.

Cytoprotective Effects of Prostaglandins and a New Potent Protease Inhibitor in Acute Pancreatitis

The redistribution of cathepsin B, a lysosomal enzyme, from the lysosomal pellet to the zymogen pellet in the subcellular fractionation, the colocalization of cathepsin B with digestive enzyme, and increased cellular, lysosomal, and mitochondrial fragility within acinar cells have been found during the early stages of caerulein-induced acute pancreatitis in rats. In the present study, the authors investigated the protective effects of prostaglandin E1 and E2, a combined therapy of these prostaglandins, and a new, synthetic, low molecular weight protease inhibitor, ONO3307, on the exocrine pancreas in this noninvasive model of experimental pancreatitis in vivo and in vitro. Prostaglandin E2, but not E1, prevented hyperamylasemia, congestion of amylase and trypsinogen in the acinar cells, redistribution of cathepsin B, and amylase and lactate dehydrogenase discharge from the dispersed acini. It also prevented cathepsin B leakage from the lysosomes and malate dehydrogenase leakage from the mitochondria in an almost dose-dependent manner, particularly at the dose of 100 micrograms/kg/hr continuous infusion. Furthermore, the combined therapy of prostaglandin E2 with ONO3307 strongly inhibited all the parameters tested in this study. This combination therapy seems to be the most effective against secretagogue-induced pancreatic injuries. These results indicate that cellular and subcellular organellar fragility seem to be closely involved in the pathogenesis of acute pancreatitis. Prostaglandin E2 seems to have important cytoprotective effects on the biologic membranes, such as a stabilizer of lysosomal or mitochondrial membranes. In addition, these findings also suggest the crucial roles of some unknown proteases in the etiology of acute pancreatitis, and indicate the clinical effectiveness of prostaglandins and this type of low molecular weight protease inhibitor for acute pancreatitis.

Role of endogenous platelet-activating factor in caerulein-induced acute pancreatitis in rats: Protective effects of a PAF-antagonist

The role of endogenous platelet-activating factor (PAF) in the pathogenesis of acute pancreatitis was investigated by determining whether CV-6209, a selective PAF antagonist, confers protection against caerulein-induced acute pancreatitis in rats. Continuous intravenous infusion of caerulein (5 micrograms/kg x h) induced time-dependent increase in serum pancreatic enzymes, pancreatic weight, and protein content of the pancreas, and produced histologic evidence of acute pancreatitis. Pretreatment with CV-6209 (1 mg/kg) significantly inhibited the elevation of serum pancreatic enzymes, pancreatic weight, and protein content of the pancreas. Caerulein-induced tissue oedema and recruitment of leucocytic cells were markedly ameliorated with CV-6209. Platelet-activating factor may be released endogenously and may play a role during acute pancreatitis.