INTERFERON GAMMA-1B IN THE TREATMENT OF COMPENSATORY ANTIINFLAMMATORYRESPONSE SYNDROME - A NEW APPROACH - PROOF OF PRINCIPLE

Background: Immunoparalysis is defined as a decrease in the level of H LA-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-inflamm atory response syndrome. Methods: Of the patients admitted consecutive ly to the intensive care unit for the management of sepsis, 10 receive d interferon gamma-1b, 100 mu g 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. R esults: Interferon gamna-1b therapy resulted in the recovery of dimini shed levels of HLA-DR expression on monocytes. Of the 10 patients, 8 r esponded to treatment within 1 day. On the first day of interferon gam ma-1b therapy, HLA-DR expression increased from mean (+/-SEM) pretreat ment levels of 27%+/-6% to 62%+/-8% (P<.01) and remained high during t he 28-day study period in 8 patients. The therapy was given to 2 patie nts a second time when HLA-DR expression on monocytes was less than 30 %. The recovery of monocytic HLA-DR expression levels after administra tion of interferon gamma-1b was associated with restitution of monocyt ic function, reflected by a significant increase of plasma interleukin -6 (P<.05) and tumor necrosis factor alpha (P<.05) levels in 9 patient s. Conclusions: This study shows that HLA-DR expression is a good mark er of compensatory anti-inflammatory response syndrome. It also shows that interferon gamma-1b not only restored the levels of HLA-DR expres sion but also reestablished the ability of monocytes to secrete the cy tokines interleukin-6 and tumor necrosis factor alpha.