title: 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: OBJECTIVE
  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-α).
  
  
  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.
authors: From the *Division of Experimental and Clinical Surgery, Department of Medicine and Biology, †Division of Immunology, and ‡Division of General Pathology, Department of Medicine and Biology, N.I. Pirogov Russian National Research Medical University, Moscow, Russia.
authors: Victor Aleksandrovitch
authors: VA
authors: Gorsky
authors: Mikhail Adnreevitch
authors: MA
authors: Agapov
authors: Marina Victorovna
authors: MV
authors: Khoreva
authors: Igor Valentinovitch
authors: IV
authors: Leonenko
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D010894:Piroxicam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D012426:Russia; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000187:drug effects* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000235:genetics; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; D016861:Cyclooxygenase Inhibitors; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D010894:Piroxicam; C059451:lornoxicam