title: Interferon gamma-1b in the treatment of compensatory anti-inflammatory response syndrome. A new approach: proof of principle.
abstract: BACKGROUND
  Immunoparalysis is defined as a decrease in the level of HLA-DR expression on monocytes during the course of sepsis.
  
  
  OBJECTIVE
  To evaluate whether interferon gamma-1b has an immunoregulatory effect in patients with immunoparalysis during the compensatory anti-inflammatory response syndrome.
  
  
  METHODS
  Of the patients admitted consecutively to the intensive care unit for the management of sepsis, 10 received interferon gamma-1b, 100 micrograms per 0.5 mL, after confirmation of HLA-DR expression of less than 30% on 2 consecutive days. The therapy was continued until HLA-DR expression remained more than 50% for 3 days.
  
  
  RESULTS
  Interferon gamma-1b therapy resulted in the recovery of diminished levels of HLA-DR expression on monocytes. Of the 10 patients, 8 responded to treatment within 1 day. On the first day of interferon gamma-1b therapy, HLA-DR expression increased from mean (+/- SEM) pretreatment levels of 27% +/- 6% to 62% +/- 8% (P < .01) and remained high during the 28-day study period in 8 patients. The therapy was given to 2 patients a second time when HLA-DR expression on monocytes was less than 30%. The recovery of monocytic HLA-DR expression levels after administration of interferon gamma-1b was associated with restitution of monocytic function, reflected by a significant increase of plasma interleukin-6 (P < .05) and tumor necrosis factor alpha (P < .05) levels in 9 patients.
  
  
  CONCLUSIONS
  This study shows that HLA-DR expression is a good marker of compensatory anti-inflammatory response syndrome. It also shows that interferon gamma-1b not only restored the levels of HLA-DR expression but also reestablished the ability of monocytes to secrete the cytokines interleukin-6 and tumor necrosis factor alpha.
authors.affiliation: Department of Anaesthesiology and Intensive Therapy, University Hospital Charité, Humboldt University, Berlin, Germany.
authors.forename: W J
authors.initials: WJ
authors.lastname: Kox
authors.forename: R C
authors.initials: RC
authors.lastname: Bone
authors.forename: D
authors.initials: D
authors.lastname: Krausch
authors.forename: W D
authors.initials: WD
authors.lastname: Döcke
authors.forename: S N
authors.initials: SN
authors.lastname: Kox
authors.forename: H
authors.initials: H
authors.lastname: Wauer
authors.forename: K
authors.initials: K
authors.lastname: Egerer
authors.forename: S
authors.initials: S
authors.lastname: Querner
authors.forename: K
authors.initials: K
authors.lastname: Asadullah
authors.forename: R
authors.initials: R
authors.lastname: von Baehr
authors.forename: H D
authors.initials: HD
authors.lastname: Volk
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D013577:Syndrome; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000998:Antiviral Agents; D006684:HLA-DR Antigens; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma