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A New Approach: Proof of Principle

Wolfgang J. Kox, MD, PhD; Roger C. Bone, MD; Dietmar Krausch, MD; Wolf-Dietrich Döcke, MD; S. Nilden Kox, PhD; Helmar Wauer, MD; Karl Egerer, MD; Susanne Querner, PhD; Khusru Asadullah, MD; Rüdiger von Baehr, MD; Hans-Dieter Volk, MD

Arch Intern Med. 1997;157(4):389-393.

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 µg 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 a (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 a.

Arch Intern Med. 1997;157:389-393

Author Affiliations
From the Department of Anaesthesiology and Intensive Therapy (Drs W. J. Kox, Krausch, S. N. Kox, Wauer, and Egerer), the Institute of Medical Immunology (Drs Döcke, Asadullah, von Baehr, and Volk), University Hospital Charité), Humboldt University, Berlin, Germany; Rush-Presbyterian-St Luke's Medical Center (Dr Bone), Chicago, Ill; and Boehringer Ingelheim GmbH (Dr Querner), Ingelheim/Rhein, Germany.

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