TY - JOUR
AU - Volk, Hans-Dieter
AB - 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 References 1. Bone RC. Sir Isaac Newton, sepsis, SIRS, and CARS . Crit Care Med. 1996;24:1125-1128.Crossref 2. Doherty GM, Lange JR, Langstein HN, et al. Evidence for IFN-gamma as a mediator of lethality of endotoxin and tumor necrosis factor-alpha . J Immunol. 1992;149:1666-1670. 3. Heinzel FP. The role of IFN-gamma in the pathology of experimental endoxemia . J Immunol. 1990;145:2920-2924. 4. Kohler J, Heumann D, Garotta G, et al. IFN-gamma involvement in the severity of gram-negative infection in mice . J Immunol. 1993; 151:916-921. 5. Redmond HP, Chavin KD, Bromberg JS, Daly JM. Inhibition of macrophage-activating cytokines is beneficial in the acute septic response . Ann Surg. 1991;214:502-508.Crossref 6. Ziegler EJ, Fisher CJ, Sprung CL, et al. Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin . N Engl J Med. 1991;324:429-436.Crossref 7. Fisher CJ, Opal SM, Dhainaut JF, et al. Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis . Crit Care Med. 1993;21:318-327.Crossref 8. Fisher CJ, Dhainaut JF, Opal SM, et al. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome: results from a randomized, double-blind, placebo-controlled trial . JAMA. 1994;271:1836-1843.Crossref 9. Dhainaut JF, Tenaillon A, Le Tulzo Y, et al. Platelet-activating factor receptor antagonist BN 52021 in the treatment of severe sepsis: a randomized, double-blind, placebo-controlled, multi-center clinical trial . Crit Care Med. 1994;22:1720-1728.Crossref 10. Bone RC. Why sepsis trials fail . JAMA. 1996; 276:565-566.Crossref 11. Luce JM. Introduction of new technology into critical care practice: a history of HA-1A human monoclonal antibody against endotoxin . Crit Care Med. 1993;21:1233-1241.Crossref 12. Platzer C, Meisel C, Vogt K, Platzer M, Volk H-D. Up-regulation of monocytic IL-10 by tumor necrosis factor-a and cAMP elevating drugs . Int Immunol. 1995;7:517-523.Crossref 13. Volk H-D, Thieme M, Heym S, et al. Alterations in function and phenotype of monocytes from patients with septic disease: predictive value and new therapeutic strategies . Behring Inst Mitt. 1991; 88:209-215. 14. Döcke WD, Syrbe U, Meinecke A, et al. Improvement of monocyte function: a new therapeutic approach? In: Reinhart K, Eyrich K, eds. Sepsis: Current Perspectives in Pathophysiology and Therapy. New York: Springer-Verlag NY Inc; 1994: 473-500. 15. International Chronic Granulomatous Disease Cooperative Study Group. A controlled trial of interferon-gamma to prevent infection in chronic granulomatous disease . N Engl J Med. 1991; 324:509-516.Crossref 16. Heath AW. Cytokines and infection . Current Opin Immunol. 1990;23:380-384.Crossref 17. Glauser MP, Zanetti G, Baumgartner JD, Cohen J. Septic shock: pathogenesis . Lancet. 1991; 338:732-736.Crossref 18. Spooner CE, Markowitz NP, Saravolatz LD. The role of tumor necrosis factor in sepsis . Clin Immunol Immunopathol. 1992;62(suppl 1, pt 13): S11-S17. 19. Beutler BA, Milsark IW, Cerami A. Passive immunization against cachetin/tumor necrosis factor protects mice from lethal effects of endotoxin . Science. 1985;229:869-871.Crossref 20. Ohlsson K, Björk P, Bergenfeldt M, Hagemann R, Thompson RC. Interleukin-1 receptor antagonist reduces mortality from endotoxic shock . Nature. 1990;348:550-552.Crossref 21. Silva AT, Bayston KF, Cohen J. Prophylactic and therapeutic effects of a monoclonal antibody to tumor necrosis factor-alpha in experimental gram-negative shock . J Infect Dis. 1990:162:421-427.Crossref 22. Tracey KJ, Fong Y, Hesse DG, et al. Anti-cachetin/ TNF monoclonal antibodies prevent septic shock during lethal bacteraemia . Nature. 1987;330:662-664.Crossref 23. Greenman RL, Schein RMH, Martin MA, et al. A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis . JAMA. 1991;266:1097-1102.Crossref 24. Wenzel R, Bone R, Fein A, et al. Results of a second double-blind, randomized, controlled trial of antiendotoxin antibody E5 in gram-negative sepsis. Presented at the 31st Inter-science Conference on Antimicrobial Agents and Chemotherapy; September 29, 1991; Chicago, Ill. 25. Bone RC. Immunologic dissonance: a continuing evolution in or understanding of the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) . Ann Intern Med. 1996;125:680-687.Crossref 26. Randow F, Syrbe U, Meisel C, et al. Mechanism of endotoxin desensitization: involvement of interleukin 10 and transforming growth factor beta . J Exp Med. 1995;181:1887-1892.Crossref 27. Volk HD, Lohmann T, Heym S, et al. Decrease of the proportion of HLA-DR+ monocytes as prognostic parameter for the clinical outcome of septic disease . In: Masihi KN, Lange W, eds. Immunotherapeutic Prospects of Infectious Disease . New York: Springer-Verlag NY Inc; 1990: 298-301. 28. Boraschi D, Censini S, Tagliabue A. Interferon-gamma reduces macrophage-suppressive activity by inhibiting prostaglandin E2 release and inducing interleukin-1 production . J Immunol. 1984; 133:264-268. 29. Chomarat P, Rissoan MC, Banchereau J, Miossec P. Interferon gamma inhibits interleukin 10 production by monocytes . J Exp Med. 1993;177:523-527.Crossref 30. Philip R, Epstein LB. Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, gamma-interferon, and interleukin-1 . Nature. 1986;323:86-89.Crossref 31. Mosmann TR, Morre KW. The role of IL-10 in cross-regulation of TH1 and TH2 responses . Immunol Today. 1991;12:A49-A53.Crossref 32. Cockfield SM, Ramassar V, Noujaim J, van der Meide PH, Halloran PF. Regulation of IFN-gamma expression in vivo: IFN-gamma up-regulates expression of its mRNA in normal and lipopolysaccharide-stimulated mice . J Immunol. 1993;150:717-725. 33. Hardy KJ, Sawada T. Human interferon-gamma strongly upregulates its own gene expression in peripheral blood lymphocytes . J Exp Med. 1989; 170:1021-1026.Crossref 34. Polk HC Jr, Cheadle WG, Livingston DH, et al. A randomised prospective clinical trial to determine the efficacy of interferon-gamma in severely injured patients . Am J Surg. 1992;163:191-196.Crossref 35. Dries DJ, Jurkovich GJ, Maier RV, et al. Effect of interferon gamma on infection-related death in patients with severe injuries . Arch Surg. 1994; 129:1031-1041.Crossref
TI - Interferon Gamma-1b in the Treatment of Compensatory Anti-inflammatory Response Syndrome: A New Approach: Proof of Principle
JF - Archives of Internal Medicine
DO - 10.1001/archinte.1997.00440250031004
DA - 1997-02-24
UR - https://www.deepdyve.com/lp/american-medical-association/interferon-gamma-1b-in-the-treatment-of-compensatory-anti-inflammatory-wUrbAcK60H
SP - 389
EP - 393
VL - 157
IS - 4
DP - DeepDyve
ER -