The Effect of Lornoxicam on TLR2 and TLR4 Messenger RNA Expression and Tumor Necrosis Factor-α, Interleukin-6, and Interleukin-8 Secretion in Patients With Systemic Complications of Acute Pancreatitis

Gorsky, Victor Aleksandrovitch; Agapov, M. A.; Хорева, М. В.; Leonenko, Igor

doi:10.1097/mpa.0000000000000344

Cited by 19 publications

(8 citation statements)

References 26 publications

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“…Despite the lack of conclusive evidence, proton pump inhibitors (PPIs) have been empirically used as the standard therapeutic method for AP in many countries worldwide, including Japan, Korea, China, Italy, and those in Eastern Europe ( Pezzilli et al, 2007 ; Hajjar et al, 2012 ; Xia et al, 2012 ; Yoo et al, 2012 ; Gorsky et al, 2015 ; Murata et al, 2015 ). PPIs act by effectively reducing the quantity of intraluminal acid in the stomach and duodenum, mechanistically by blocking the common terminal pathway for acid secretion, which lies at the H + -K + -adenosine triphosphatase (ATPase) ( Robinson, 2004 ).…”

Section: Introductionmentioning

confidence: 99%

Proton Pump Inhibitors Were Associated With Reduced Pseudocysts in Acute Pancreatitis: A Multicenter Cohort Study

et al. 2021

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Background: Acute pancreatitis (AP) is a systemic inflammatory disorder with a wide spectrum of clinical symptoms that can range from mild to severe. Previous preclinical study results suggest that proton pump inhibitors (PPIs) can inhibit exocrine pancreatic secretion and exert anti-inflammatory properties, which might in turn improve the outcome of AP.Aim: We conducted this multicenter, retrospective cohort study to investigate the potential effects of PPIs on the mortality, and total duration of hospital stay and local complication occurrence of patients with AP.Methods: A total of 858 patients with AP were included. All patients presented to the hospital within 48 h of symptom onset and were divided into the following two groups: patients who were treated with PPIs (n = 684) and those not treated with PPIs (n = 174). We used propensity score matching (PSM) analysis to reduce confounding bias before comparing the outcomes between the two groups.Results: Before PSM analysis, there were significant differences in a number of parameters between the two groups, including age, sex, hematocrit, blood urea nitrogen, peritonitis signs, Ranson’s score, and Acute Physiology Chronic Health Evaluation II score and organ failure occurrence. Before PSM, the PPIs group had a higher rate of mortality than the control group [RR = 1.065; 95% confidence ratio (CI) 1.045–1.086; p = 0.001]. After PSM, there was no significant difference in mortality (RR = 1.009; 95% CI, 0.999–1.019; p = 0.554) or total hospital stay (p = 0.856), although the PPIs group had a lower occurrence of pancreatic pseudocyst (RR = 0.416; 95% CI 0.221–0.780; p = 0.005).Conclusion: This study showed that PPIs therapy was not associated with reduced mortality or total hospital stay, but was associated with a reduction in the occurrence of pseudocysts in patients with acute pancreatitis.

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Section: Introductionmentioning

confidence: 99%

Proton Pump Inhibitors Were Associated With Reduced Pseudocysts in Acute Pancreatitis: A Multicenter Cohort Study

et al. 2021

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“…There were no differences in TLR4 expression between MAP and SAP, however these findings may have been confounded by the use of empiric glucocorticoids in the SAP cohort. These findings are supported by studies of mRNA derived from PBMCs that found high levels of TLR4 and TLR2 transcripts in AP as compared to healthy controls ( 49 , 181 ). In summary, all three studies suggest higher TLR4 activity in AP compared to controls, however they do not determine whether TLR4 expression differs between mild and severe disease.…”

Section: Innate Immune and Inflammatory Responses In Apmentioning

confidence: 53%

Fire in the belly: A scoping review of the immunopathological mechanisms of acute pancreatitis

Venkatesh

Glenn²,

Delaney³

et al. 2023

Front. Immunol.

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IntroductionAcute pancreatitis (AP) is characterised by an inflammatory response that in its most severe form can cause a systemic dysregulated immune response and progression to acute multi-organ dysfunction. The pathobiology of the disease is unclear and as a result no targeted, disease-modifying therapies exist. We performed a scoping review of data pertaining to the human immunology of AP to summarise the current field and to identify future research opportunities.MethodsA scoping review of all clinical studies of AP immunology was performed across multiple databases. Studies were included if they were human studies of AP with an immunological outcome or intervention.Results205 studies met the inclusion criteria for the review. Severe AP is characterised by significant immune dysregulation compared to the milder form of the disease. Broadly, this immune dysfunction was categorised into: innate immune responses (including profound release of damage-associated molecular patterns and heightened activity of pattern recognition receptors), cytokine profile dysregulation (particularly IL-1, 6, 10 and TNF-α), lymphocyte abnormalities, paradoxical immunosuppression (including HLA-DR suppression and increased co-inhibitory molecule expression), and failure of the intestinal barrier function. Studies including interventions were also included. Several limitations in the existing literature have been identified; consolidation and consistency across studies is required if progress is to be made in our understanding of this disease.ConclusionsAP, particularly the more severe spectrum of the disease, is characterised by a multifaceted immune response that drives tissue injury and contributes to the associated morbidity and mortality. Significant work is required to develop our understanding of the immunopathology of this disease if disease-modifying therapies are to be established.

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“…Knockdown of MYD88 attenuates LPS-induced inflammatory responses in pancreatic ductal cells (24). Meanwhile, acute pancreatitis patients have high level of TLR4 and decreasing the expression of TLR4 reduces the risk of systemic complications and mortality (25). NF-κB and p38MAPK are the two main signaling pathways activated by TLR4-mediated signaling, and both play an important role in the regulation of several inflammatory cytokines and mediators.…”

Section: Discussionmentioning

confidence: 99%

Phosphoinositide 3‑kinase/protein kinase B regulates inflammation severity via signaling of Toll‑like receptor 4 in severe acute pancreatitis

Wang

Zhang

et al. 2018

Mol Med Report

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Phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) has been indicated to serve an important role in the pathogenesis of inflammatory diseases. It was previously demonstrated that the PI3K/Akt inhibitor wortmannin alleviated the severity of inflammation and improved the survival rate in rats with induced severe acute pancreatitis (SAP), which indicates that PI3K/Akt may serve a role in the pathogenesis of acute pancreatitis. To date, the mechanism by which PI3K/Akt regulates inflammation has not been elucidated. In the present study, it was hypothesized that PI3K/Akt may be invovled in SAP inflammation via regulation of the Toll‑like receptor 4 (TLR4) signaling pathway. Rats with SAP were treated with the PI3K/Akt agonist insulin‑like growth factor (IGF)‑1, which alleviated the severity of inflammation in a dose‑dependent manner. Furthermore, to better understand the role of PI3K/Akt in inflammation, RAW264.7 murine macrophages were stimulated with IGF‑1 and wortmannin alone or together before the induction of inflammation by treatment with lipopolysaccharide (LPS). The results indicated that LPS stimulated overexpression of TLR4, myeloid differentiation primary response gene 88 (MyD88), PI3K, Akt, p38MAPK and NF‑κBp65 mRNA, and increased the levels of tumor necrosis factor (TNF)‑α and interleukin (IL)‑6 in RAW264.7 cells compared with the control group. The levels of all detected factors were increased by stimulation with IGF‑1, whereas these levels were decreased following treatment with wortmannin alone, and the effect of IGF‑1 was abolished by wortmannin in RAW264.7 cells. In vivo studies indicated that IGF‑1 produced the same anti‑inflammatory effect as wortmannin and that expression of TLR4, p38MAPK and NF‑κBp65 decreased following treatment with IGF‑1. These findings indicate that PI3K/Akt may take part in the progression of SAP by regulating the TLR4 signaling pathway and that IGF‑1 can inhibit inflammation in SAP rats.

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The Effect of Lornoxicam on TLR2 and TLR4 Messenger RNA Expression and Tumor Necrosis Factor-α, Interleukin-6, and Interleukin-8 Secretion in Patients With Systemic Complications of Acute Pancreatitis

Abstract: The use of lornoxicam at the onset of acute pancreatitis decreased TLR2 and TLR4 expression and the production of proinflammatory cytokines, thereby reducing the risk of systemic complications and mortality.

Cited by 19 publications

References 26 publications

Proton Pump Inhibitors Were Associated With Reduced Pseudocysts in Acute Pancreatitis: A Multicenter Cohort Study

Proton Pump Inhibitors Were Associated With Reduced Pseudocysts in Acute Pancreatitis: A Multicenter Cohort Study

Fire in the belly: A scoping review of the immunopathological mechanisms of acute pancreatitis

Phosphoinositide 3‑kinase/protein kinase B regulates inflammation severity via signaling of Toll‑like receptor 4 in severe acute pancreatitis

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