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

被引:24
|
作者
Gorsky, Victor Aleksandrovitch [1 ]
Agapov, Mikhail Adnreevitch [1 ]
Khoreva, Marina Victorovna [2 ]
Leonenko, Igor Valentinovitch [3 ]
机构
[1] NI Pirogov Russian Natl Res Med Univ, Dept Med & Biol, Div Expt & Clin Surg, Moscow, Russia
[2] NI Pirogov Russian Natl Res Med Univ, Div Immunol, Dept Med & Biol, Moscow, Russia
[3] NI Pirogov Russian Natl Res Med Univ, Div Gen Pathol, Dept Med & Biol, Moscow, Russia
关键词
acute pancreatitis; lornoxicam; COX inhibition; toll-like receptors; proinflammatory cytokines; NF-KAPPA-B; LUNG INJURY; MICE; SEVERITY; INFLAMMATION; TOLL-LIKE-RECEPTOR-4; CHLOROQUINE; INHIBITION; LIGANDS; SEPSIS;
D O I
10.1097/MPA.0000000000000344
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Objectives To assess the effects of the cyclooxygenase-1/cyclooxygenase-2 inhibitor lornoxicam on systemic complications in patients with acute pancreatitis, Toll-like receptor (TLR)2 and TLR4 messenger RNA expression, and cytokine secretion (IL-6, IL-8, tumor necrosis factor-). Methods Adult patients with acute pancreatitis were randomized to standard therapy or standard therapy plus lornoxicam. Standard therapy included analgesics, spasmolytics, octreotide, pantoprazole, and intravenous fluids. The TLR2 and TLR4 expression levels and TLR2- and TLR4-mediated cytokine production in peripheral blood mononuclear cells were assessed in patients with severe complications and in healthy volunteers (n = 15). Results A total of 334 patients received standard therapy (n = 246) or standard therapy plus lornoxicam (n = 88), 172 (51.5%) of whom developed systemic complications. Occurrence of complications was higher with standard therapy compared with lornoxicam (57.3% versus 35.2%; P = 0.00034), as was mortality (19.1% versus 6.8%; P = 0.006). The TLR2 and TLR4 expression and TLR2 and TLR4-mediated cytokine production were significantly higher in patients with systemic complications of acute pancreatitis compared with healthy volunteers. Relative TLR2 expression and cytokine production were significantly reduced in patients receiving lornoxicam versus standard therapy. Conclusions 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.
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页码:824 / 830
页数:7
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