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C1-inhibitor substitution therapy in septic shock and in the vascular leak syndrome induced by high doses of interleukin-2

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Abstract

C1-inhibitor (C1-INH) is the major plasma inhibitor of the complement and contact systems. Activation of either system has been shown to occur in patients with septic shock and is associated with a poor outcome. Functional levels of C1-INH tend to be normal in septic patients although paradoxically this inhibitor is an acute phase protein. Moreover, levels of proteolytically inactivated C1-INH are increased in sepsis pointing to an increased turn-over. These observations suggest a relative deficiency of biologically active C1-INH in sepsis. Complement and contact activation have also been shown to occur in the vascular leak syndrome (VLS) induced by immunotherapy with the cytokine interleukin-2 (IL-2), which syndrome may be regarded as a human model for septic shock. The similarity between VLS and sepsis encompasses more than complement and contact activation since a number of other inflammatory mediators considered to play a role in the pathogenesis of septic shock, are also involved in the development of VLS. The role and the mechanisms of complement and contact activation in sepsis and in the VLS are reviewed in this paper. Initial results of intervention therapy with high doses of C1-INH in these syndromes are also reported. It is concluded that high doses of C1-INH can be safely administered to patients with septic shock or with VLS and may attenuate complement and contact activation in these conditions. Double-blind controlled studies are needed to definitely prove these effects and to establish whether this treatment is able to reduce mortality and morbidity of these syndromes.

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Author notes

  1. A. C. Ogilvie

    Present address: Department of Internal Medicine, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

Authors and Affiliations

  1. Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, P.O. Box 9406, NL-1006 AK, Amsterdam, The Netherlands

    C. E. Hack (c/o Publication Secretariat) & A. J. M. Eerenberg

  2. Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands

    A. J. M. Eerenberg

  3. Medical Intensive Care Unit, Free University Hospital, Amsterdam, The Netherlands

    A. C. Ogilvie & L. G. Thijs

  4. Behringwerke AG, Marburg, Germany

    B. Eisele

  5. Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands

    J. Wagstaff

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  1. C. E. Hack
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  4. A. J. M. Eerenberg
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  5. J. Wagstaff
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  6. L. G. Thijs
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Hack, C.E., Ogilvie, A.C., Eisele, B. et al. C1-inhibitor substitution therapy in septic shock and in the vascular leak syndrome induced by high doses of interleukin-2. Intensive Care Med 19 (Suppl 1), S19–S28 (1993). https://doi.org/10.1007/BF01738946

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