Features of Postoperative Immune Suppression Are Reversible With Interferon Gamma and Independent of Interleukin-6 Pathways. Issue 2 (August 2016)

• Record Type: Journal Article
• Authors: Longbottom, E. Rebecca; Torrance, Hew D. T.; Owen, Helen C.; Fragkou, Paraskevi C.; Hinds, Charles J.; Pearse, Rupert M.; O'Dwyer, Michael J.
• Is Part Of: Annals of surgery. Volume 264:Issue 2(2016:Aug.)
• Page Start: 370
• Page End: 377
• Publication Date: 2016-08
• Subjects: gastrointestinal surgery -- IL-6 -- immunoparalysis -- interferon gamma; Surgery -- Periodicals; 617.005
• DOI: 10.1097/SLA.0000000000001484
• Languages: English
• ISSNs: 0003-4932

Abstract

Abstract : Supplemental Digital Content is available in the text Abstract: Objective: The aim of this study was to evaluate the role of interleukin (IL)-6 pathways in postoperative immune suppression and to assess the reversibility of this phenomenon. Background: The postoperative period is characterized by increased IL-6 production and features of immune suppression. In vitro, IL-6 mediates anti-inflammatory effects through inhibition of interferon gamma (IFN-γ) pathways. The significance of the immunomodulatory effects of IL-6 in the clinical setting of postoperative immune suppression remains unclear. Methods: Patients over 45 years old undergoing elective surgery, involving the gastrointestinal tract, were recruited. IL-6 levels were assayed using an enzyme linked immunosorbent assay preoperatively, and at 24 and 48 hours. Peripheral blood mononuclear cells from healthy volunteers were cultured in perioperative serum and CD14 + Human Leukocyte Antigen-DR (HLA-DR) [monocyte HLA-DR (mHLA-DR)] geometric mean florescent intensity was measured in the presence and absence of IL-6 neutralizing antibody and recombinant IFN-γ. Results: Of the 108 patients, 41 developed a postoperative infection. The IL-6 levels increased 19-fold from the preoperative sample to 24 hours postoperatively ( P < 0.0001). Higher IL-6 levels at 24 ( P = 0.0002) and 48 hours ( P = 0.003) were associated with subsequent postoperative infectious complications. mHLA-DR mean florescent intensity fell when healthy peripheral blood mononuclear cells were cultured with postoperative serum compared with preoperative serum ( P = 0.008). This decrease was prevented by the presence of IFN-γ in the culture media, but not by the presence of IL-6-neutralizing antibody. Conclusions: IL-6 levels increase after a major surgery and are associated with an increased susceptibility to postoperative infections. Serum obtained from postoperative patients induces an immunosuppressive response, reflected in reduced mHLA-DR levels, mediated through IL-6 independent pathways and is reversible with IFN-γ. These data may have therapeutic implications for the prevention of infection in patients undergoing major surgery.