title: IL6 trans-signaling promotes functional recovery of hypofunctional phagocytes through STAT3 activation during peritonitis.
abstract: OBJECTIVE
  The role of high interleukin 6 (IL6) levels has not been clearly explained in severe sepsis. We show that the augmentation of the IL6 signal by recombinant IL6 receptors (rIL6R) delivery allows the functional recovery of phagocytes in a peritonitis mouse model.
  
  
  METHODS
  Mice were challenged intraperitoneally (i.p.) with live Staphylococcus aureus for effect of IL6R delivery on the 24 h-survival, bacterial clearance and cellular responses. In additional experiments to assess the effect of IL6R delivery on phagocytosis, the model was i.p. inoculated with heat-killed S. aureus with or without rIL6R and the peritoneal lavage fluid and cells were collected at 1 h after the i.p. inoculation of S. aureus.
  
  
  RESULTS
  The IL6R delivery tended to improve 24 h survival and increase bacteria clearance from the septic mice. The rIL6R treatment to heat-killed bacteria challenged mice augmented the uptake of bacteria and phagosome acidification, inducing the phosphorylation of STAT3 in peritoneal cells within 1 h after the IL6R delivery. Furthermore, the rIL6R delivery prevented the extracellular release of neutrophil elastase activity and myeloperoxidase (harmful factors).
  
  
  CONCLUSIONS
  These results indicate that augmentation of IL6 signaling appears to be critical for the effective management of hypofunctional neutrophils during severe inflammation, such as sepsis.
authors.affiliation: Medical Technology Education Unit, Kyorin University Faculty of Health Sciences, 476 Miyashita, Hachioji, Tokyo 192-8508, Japan. onogawa@ks.kyorin-u.ac.jp
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Onogawa
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Saito-Taki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Takako
authors.initials: T
authors.lastname: Wada
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D010538:Peritonitis / Q000276:immunology*; D010586:Phagocytes / Q000276:immunology*; D019947:Receptors, Interleukin-6 / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D050796:STAT3 Transcription Factor / Q000276:immunology*; D015398:Signal Transduction; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse