title: Enhanced expression of intracellular heme oxygenase-1 in deactivated monocytes from patients with severe systemic inflammatory response syndrome.
abstract: BACKGROUND
  Monocyte deactivation is an important contributor to infectious susceptibility in critically ill patients. However, the mechanism of monocyte deactivation has not been fully elucidated. Recently, intracellular heme oxygenese-1 (HO-1), an anti-inflammatory heat-shock protein, was reported to be activated by Toll-like receptors (TLRs), and to inhibit inflammatory cytokine production such as that of TNF-alpha. In the present study, we evaluated the expression of intracellular HO-1 and TLRs in monocytes from patients with severe systemic inflammatory response syndrome (SIRS) and examined the role of HO-1 in monocyte deactivation.
  
  
  METHODS
  Twenty-seven patients who fulfilled the criteria for severe SIRS and had a serum C-reactive protein (CRP) level >10 mg/dL were included in this study. The cause of SIRS was sepsis in 16 patients, trauma in 7, and other in 4. Expression of intracellular HO-1, surface TLR2 and TLR4, and intracellular cytokines (TNF-alpha, Interleukin-6) stimulated via TLR activation were measured in circulating monocytes by flow cytometry. Intracellular HO-1 expression was evaluated in normal monocytes stimulated with patient serum. Serum cytokine levels were also measured. Patient data were compared with data from healthy volunteers (n = 16).
  
  
  RESULTS
  Cytoplasmic HO-1 was clearly detected by fluorescence microscopy. Expression of HO-1, TLR2, and TLR4 in monocytes was significantly enhanced in patients with severe SIRS compared with that in healthy volunteers, whereas intracellular TNF-alpha expression with peptidoglycan was significantly decreased (p < 0.05) in patients compared with that in healthy volunteers. HO-1 expression was significantly enhanced in normal monocytes stimulated with patient serum. Intracellular HO-1 levels were positively related to serum TNF-alpha levels in patients (r = 0.46).
  
  
  CONCLUSIONS
  Expression of intracellular HO-1 and of TLRs was enhanced in deactivated monocytes from patients with SIRS. Increased production of intracellular HO-1 in response to serum factors may play a role in monocyte deactivation after systemic inflammation.
authors.affiliation: Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medical, Osaka, Japan. mouri@hp-emerg.med.osaka-u.ac.jp
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Mohri
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ogura
authors.forename: Taichin
authors.initials: T
authors.lastname: Koh
authors.forename: Kieko
authors.initials: K
authors.lastname: Fujita
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sumi
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yoshiya
authors.forename: Asako
authors.initials: A
authors.lastname: Matsushima
authors.forename: Hideo
authors.initials: H
authors.lastname: Hosotsubo
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kuwagata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimazu
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sugimoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015601:Injury Severity Score; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007378:Interleukins; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D051547:Heme Oxygenase-1