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. MATERIALS AND 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.
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 peritonitismouse model. MATERIALS AND 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: W K Eddie Ip; Anna Sokolovska; Guillaume M Charriere; Laurent Boyer; Stephanie Dejardin; Michael P Cappillino; L Michael Yantosca; Kazue Takahashi; Kathryn J Moore; Adam Lacy-Hulbert; Lynda M Stuart Journal: J Immunol Date: 2010-05-17 Impact factor: 5.422
Authors: J T Frieling; M van Deuren; J Wijdenes; J W van der Meer; C Clement; C J van der Linden; R W Sauerwein Journal: J Infect Dis Date: 1995-02 Impact factor: 5.226
Authors: Ceri A Fielding; Rachel M McLoughlin; Louise McLeod; Chantal S Colmont; Meri Najdovska; Dianne Grail; Matthias Ernst; Simon A Jones; Nicholas Topley; Brendan J Jenkins Journal: J Immunol Date: 2008-08-01 Impact factor: 5.422
Authors: Maria L Valle; Janine Dworshak; Ashok Sharma; Ahmed S Ibrahim; Mohamed Al-Shabrawey; Shruti Sharma Journal: Exp Eye Res Date: 2018-09-18 Impact factor: 3.467