Interferon gamma-1b in the treatment of compensatory anti-inflammatory response syndrome. A new approach: proof of principle

Arch Intern Med. 1997 Feb 24;157(4):389-93.

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.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Female
  • HLA-DR Antigens / metabolism*
  • Humans
  • Inflammation / immunology*
  • Interferon-gamma / therapeutic use*
  • Interleukin-6 / biosynthesis
  • Male
  • Middle Aged
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Syndrome
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Antiviral Agents
  • HLA-DR Antigens
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma