Interferon gamma-1b in the treatment of compensatory anti-inflammatory response syndrome. A new approach: proof of principle.
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.
Kox
W J
WJ
Department of Anaesthesiology and Intensive Therapy, University Hospital Charité, Humboldt University, Berlin, Germany.
Bone
R C
RC
Krausch
D
D
Döcke
W D
WD
Kox
S N
SN
Wauer
H
H
Egerer
K
K
Querner
S
S
Asadullah
K
K
von Baehr
R
R
Volk
H D
HD
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
D000998:Antiviral Agents; D006684:HLA-DR Antigens; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma