scholarly journals A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits

Gut ◽  
1998 ◽  
Vol 43 (2) ◽  
pp. 232-239 ◽  
Author(s):  
M O Osman ◽  
J U Kristensen ◽  
N O Jacobsen ◽  
S B Lausten ◽  
B Deleuran ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Severe Acute Pancreatitis ◽  
Pancreatic Necrosis ◽  
Interleukin 8 ◽  
Systemic Complications ◽  
Duct Ligation ◽  
Tnf Α

Background—Interleukin 8 (IL-8) has recently been proposed to have an important role in mediating the development of the systemic sequelae associated with severe acute pancreatitis.Aims—To define the role of IL-8 in acute pancreatitis by neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbit model of severe acute pancreatitis.Methods—Acute pancreatitis was induced by retrograde injection of 5% chenodeoxycholic acid into the pancreatic duct and duct ligation. Twenty rabbits were divided equally into two groups: acute pancreatitis controls received physiological saline and the treated group received WS-4, 30 minutes before induction of acute pancreatitis.Results—Pretreatment of animals with WS-4 resulted in significant down regulation of serum IL-8 and tumour necrosis factor α (TNF-α) from three to six hours after induction of acute pancreatitis (p=0.011 and 0.047 for IL-8 and 0.033 and 0.022 for TNF-α, respectively). In addition, a significant reduction in the CD11b and CD18 positive cells and the amount of interstitial neutrophil infiltration in the lungs from WS-4 treated animals was seen. In contrast, WS-4 did not alter the amount of pancreatic necrosis and the serum concentrations of amylase, lipase, calcium, and glucose.Conclusion—WS-4 cannot change the amount of pancreatic necrosis induced by injection of 5% bile acid, but does reduce the acute lung injury, presumably through inhibition of circulating IL-8 and TNF-α, and CD11b/CD18 in lung tissue. Therefore, a role of IL-8 in the progression of acute pancreatitis and the development of its systemic complications is suggested.

scholarly journals Pathophysiological aspects of severe acute pancreatitis-associated lung injury

2005 ◽  
Vol 133 (1-2) ◽  
pp. 76-81 ◽  
Author(s):  
Maja Surbatovic ◽  
Krsta Jovanovic ◽  
Sonja Radakovic ◽  
Nikola Filipovic
Keyword(s):  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Mortality Rate ◽  
Lung Injury ◽  
Severe Acute Pancreatitis ◽  
Distress Syndrome ◽  
Severe Form ◽  
Very High ◽  
Intensive Medicine

Acute pancreatitis is an inflammatory process which occurs in severe form in 20% of all patients, out of whom 1596-25% will die. The incidence of severe acute pancreatitis-associated lung injury (APALI) varies from 15% to 55% and its severity varies from mild hypoxemia to acute respiratory distress syndrome (ARDS). Acute lung injury (ALI) and ARDS are the most significant manifestations of extra abdominal dysfunctions in severe acute pancreatitis with mortality rate as high as 60% in the first week of the onset of illness. Different pathophysiological mechanisms of severe acute pancreatitis-associated lung injury have been described. The role of enzymes, adhesion molecules, neutrophils, fibronectin and various inflammatory mediators has been emphasized. Mechanism of the acute lung injury associated with the acute pancreatitis is very complex and has not been clear yet. There is no specific therapeutic procedure and mortality rate is very high. Therefore, further studies are necessary to address this acute and growing problem in intensive medicine.

scholarly journals Shenmai injection alleviates acute lung injury in a severe acute pancreatitis rat model via heme oxygenase-1 upregulation

2020 ◽  
Author(s):  
Fei-hu Zhang ◽  
Hao Hao ◽  
Yang Liu ◽  
Kai-liang Fan ◽  
Wen Dai ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Severe Acute Pancreatitis ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Mrna Levels ◽  
Tissue Samples ◽  
Shenmai Injection ◽  
Tnf Α

Abstract Background: To determine the effect of Shenmai injection (SMI) on acute lung injury (ALI) induced by severe acute pancreatitis (SAP) in rats. Methods: Forty male Sprague-Dawley (SD) rats were grouped into 4 categories: SAP group, sham surgery (SS) group, SAP + SMI group, SAP + SMI + Zinc protoporphyrin (ZnPP) group. Rats in the SAP group were intravenously injected with 1.6 ml/kg saline 30 minutes after induction of SAP models. Rats in the SAP + SMI group were intravenously injected with 1.6 ml/kg SMI, while those in the SAP + SMI + ZnPP group rats were intravenously injected with 1.6 ml/kg SMI and 30 mg/kg ZnPP via intraperitoneal injection. Twenty-four hours after SAP induction, the rats were sacrificed. Excised lung tissues were histologically examined, protein concentration in bronchoalvelar lavage fluid (BALF) was measured and lung wet-to-dry (W/D) weight ratio was calculated. The protein and mRNA levels of the tumor necrosis factor (TNF) -α, heme oxygenase (HO) -1 and interleukin (IL) -10 in blood and tissue samples were measured.Results: SMI treatment attenuated SAP-induced ALI as evidenced by lower scores of lung damage compared with untreated SAP group (p＜0.05). SMI also abolished the SAP-induced rise in BALF and W/D ratio protein concentrations (p＜0.05). Moreover, SMI treatment increased HO-1, IL-10 levels but decreased TNF-α level in serum and tissue samples (p＜0.05). However, inhibition of HO-1 expression by ZnPP led to significant inhibition of all the changes.Conclusions: SMI can alleviate SAP-induced ALI through HO-1 upregulation.

scholarly journals Shenmai injection alleviates acute lung injury in a severe acute pancreatitis rat model via heme oxygenase-1 upregulation

2020 ◽  
Author(s):  
Fei-hu Zhang ◽  
Hao Hao ◽  
Yang Liu ◽  
Kai-liang Fan ◽  
Wen Dai ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Severe Acute Pancreatitis ◽  
Histological Evaluation ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Tissue Samples ◽  
Shenmai Injection ◽  
Tnf Α

Abstract Objective To determine the effect of Shenmai injection (SMI) on acute lung injury (ALI) induced by severe acute pancreatitis (SAP) in rats. Methods 40 male SD (Sprague-Dawley) rats were grouped into 4 categories: SAP group, sham surgery (SS) group, SAP + SMI group, SAP + SMI + Zinc protoporphyrin (ZnPP) group. 30 minutes after induction of SAP, the SAP group rats were intravenously injected with 1.6 ml/kg saline, the SAP + SMI group rats were intravenously injected with 1.6 ml/kg SMI, while the SAP + SMI + ZnPP group rats were intravenously injected with 1.6 ml/kg SMI and 30 mg/kg ZnPP via intraperitoneal injection. 24 hours after SAP induction, the rats were sacrificed. Histological evaluation of the lung tissues, protein concentration in BALF and lung wet-to-dry (W/D) weight ratio were determined and analyzed. Blood and tissue samples were also collected to determine the levels of protein expression and mRNA of the tumor necrosis factor (TNF) -α, HO-1 and interleukin (IL) -10. Results Compared to the SAP group, SAP-induced ALI was significantly attenuated by SMI treatment and had a lower score of lung damage severity ( p <0.05). SMI significantly attenuated the SAP-induced rise in BALF and W/D ratio protein concentrations ( p <0.05). The SMI treatment resulted in a statistically significant increase of HO-1, IL-10 levels and a significant reduction of TNF-α level in both serum and tissue samples ( p <0.05). However, inhibition of HO-1 expression by ZnPP led to significant inhibition of all the changes. Conclusions SMI can alleviate SAP-induced ALI through HO-1 upregulation.

scholarly journals Shenmai injection alleviates acute lung injury in a severe acute pancreatitis rat model via heme oxygenase-1 upregulation

2021 ◽  
Author(s):  
Fei-hu Zhang ◽  
Hao Hao ◽  
Yang Liu ◽  
Kai-liang Fan ◽  
Wen Dai ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Severe Acute Pancreatitis ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Mrna Levels ◽  
Tissue Samples ◽  
Shenmai Injection ◽  
Tnf Α

Abstract Background: To determine the effect of Shenmai injection (SMI) on acute lung injury (ALI) induced by severe acute pancreatitis (SAP) in rats. Methods: Forty male Sprague-Dawley (SD) rats were grouped into 4 categories: SAP group, sham surgery (SS) group, SAP + SMI group, SAP + SMI + Zinc protoporphyrin (ZnPP) group. Rats in the SAP group were intravenously injected with 1.6 ml/kg saline 30 minutes after induction of SAP models. Rats in the SAP + SMI group were intravenously injected with 1.6 ml/kg SMI, while those in the SAP + SMI + ZnPP group rats were intravenously injected with 1.6 ml/kg SMI and 30 mg/kg ZnPP via intraperitoneal injection. Twenty-four hours after SAP induction, the rats were sacrificed. Excised lung tissues were histologically examined, protein concentration in bronchoalvelar lavage fluid (BALF) was measured and lung wet-to-dry (W/D) weight ratio was calculated. The protein and mRNA levels of the tumor necrosis factor (TNF) -α, heme oxygenase (HO) -1 and interleukin (IL) -10 in blood and tissue samples were measured.Results: SMI treatment attenuated SAP-induced ALI as evidenced by lower scores of lung damage compared with untreated SAP group (p＜0.05). SMI also abolished the SAP-induced rise in BALF and W/D ratio protein concentrations (p＜0.05). Moreover, SMI treatment increased HO-1, IL-10 levels but decreased TNF-α level in serum and tissue samples (p＜0.05). However, inhibition of HO-1 expression by ZnPP led to significant inhibition of all the changes.Conclusions: SMI can alleviate SAP-induced ALI through HO-1 upregulation.

scholarly journals Phospholipase C-ε signaling mediates endothelial cell inflammation and barrier disruption in acute lung injury

2016 ◽  
Vol 311 (2) ◽  
pp. L517-L524 ◽  
Author(s):  
Kaiser M. Bijli ◽  
Fabeha Fazal ◽  
Spencer A. Slavin ◽  
Antony Leonard ◽  
Valerie Grose ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Phospholipase C ◽  
Phorbol Esters ◽  
Critical Determinant ◽  
Monocyte Chemoattractant Protein 1 ◽  
Barrier Disruption ◽  
Proinflammatory Mediators ◽  
Tnf Α

Phospholipase C-ε (PLC-ε) is a unique PLC isoform that can be regulated by multiple signaling inputs from both Ras family GTPases and heterotrimeric G proteins and has primary sites of expression in the heart and lung. Whereas the role of PLC-ε in cardiac function and pathology has been documented, its relevance in acute lung injury (ALI) is unclear. We used PLC-ε−/− mice to address the role of PLC-ε in regulating lung vascular inflammation and injury in an aerosolized bacterial LPS inhalation mouse model of ALI. PLC-ε−/− mice showed a marked decrease in LPS-induced proinflammatory mediators (ICAM-1, VCAM-1, TNF-α, IL-1β, IL-6, macrophage inflammatory protein 2, keratinocyte-derived cytokine, monocyte chemoattractant protein 1, and granulocyte-macrophage colony-stimulating factor), lung neutrophil infiltration and microvascular leakage, and loss of VE-cadherin compared with PLC-ε+/+ mice. These data identify PLC-ε as a critical determinant of proinflammatory and leaky phenotype of the lung. To test the possibility that PLC-ε activity in endothelial cells (EC) could contribute to ALI, we determined its role in EC inflammation and barrier disruption. RNAi knockdown of PLC-ε inhibited NF-κB activity in response to diverse proinflammatory stimuli, thrombin, LPS, TNF-α, and the nonreceptor agonist phorbol 13-myristate 12-acetate (phorbol esters) in EC. Depletion of PLC-ε also inhibited thrombin-induced expression of NF-κB target gene, VCAM-1. Importantly, PLC-ε knockdown also protected against thrombin-induced EC barrier disruption by inhibiting the loss of VE-cadherin at adherens junctions and formation of actin stress fibers. These data identify PLC-ε as a novel regulator of EC inflammation and permeability and show a hitherto unknown role of PLC-ε in the pathogenesis of ALI.

scholarly journals Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Limei Wan ◽  
Weibin Wu ◽  
Shunjun Jiang ◽  
Shanhe Wan ◽  
Dongmei Meng ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Calcium Channel ◽  
Lavage Fluid ◽  
Cell Number ◽  
Effector Cells ◽  
Potent Inhibition ◽  
Tnf Α ◽  
Calcium Channel Inhibitors

Recent studies have illuminated that blocking Ca2+ influx into effector cells is an attractive therapeutic strategy for lung injury. We hypothesize that T-type calcium channel may be a potential therapeutic target for acute lung injury (ALI). In this study, the pharmacological activity of mibefradil (a classical T-type calcium channel inhibitor) was assessed in a mouse model of lipopolysaccharide- (LPS-) induced ALI. In LPS challenged mice, mibefradil (20 and 40 mg/kg) dramatically decreased the total cell number, as well as the productions of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). Mibefradil also suppressed total protein concentration in BALF, attenuated Evans blue extravasation, MPO activity, and NF-κB activation in lung tissue. Furthermore, flunarizine, a widely prescripted antimigraine agent with potent inhibition on T-type channel, was also found to protect mice against lung injury. These data demonstrated that T-type calcium channel inhibitors may be beneficial for treating acute lung injury. The important role of T-type calcium channel in the acute lung injury is encouraged to be further investigated.

Effects of penehyclidine hydrochloride on severe acute pancreatitis-associated acute lung injury in rats

2018 ◽  
Vol 97 ◽  
pp. 1689-1693 ◽  
Author(s):  
Rongtao Zhu ◽  
Yipu Zhao ◽  
Xiaobo Li ◽  
Tao Bai ◽  
Shuai Wang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Severe Acute Pancreatitis ◽  
Penehyclidine Hydrochloride
Sign in / Sign up

Export Citation Format

Share Document