Intensive Care Medicine

, Volume 22, Supplement 4, pp S474–S481

Monocyte deactivation-rationale for a new therapeutic strategy in sepsis

  • H. -D. Volk
  • P. Reinke
  • D. Krausch
  • H. Zuckermann
  • K. Asadullah
  • J. M. Müller
  • W. -D. Döcke
  • W. J. Kox
Original

DOI: 10.1007/BF01743727

Cite this article as:
Volk, H.-., Reinke, P., Krausch, D. et al. Intensive Care Med (1996) 22: S474. doi:10.1007/BF01743727

Abstract

Inflammatory cells, in particular monocytes/macrophages, release pro-inflammatory mediators in response to several infectious and non-infectious stimuli. The excessive release of these mediators, resulting in the development of whole body inflammation, may play an important role in the pathogenesis of sepsis and septic shock. TNF-alpha, acting synergistically with cytokines such as IL-1, GM-CSF and IFN-gamma, is the key mediator in the induction process of septic shock, as shown in several experimental models. Based on this concept and on the encouraging results obtained in several experimental models, a number of clinical sepsis trials targeting the production or action of TNF-alpha or IL-1 have been performed in recent years. Unfortunately, these trials have failed to demonstrate a therapeutic benefit. One reason for this may be the lack of exact immunologic analyses during the course of septic disease. Recently, we demonstrated that there is a biphasic immunologic response in sepsis: an initial hyperinflammatory phase is followed by a hypo-inflammmatory one. The latter is associated with immunodeficiency which is characterized by monocytic deactivation, which we have called “immunoparalysis”. While anti-inflammatory therapy (e.g. anti-TNF antibodies, IL-1 receptor antagonist, IL-10) makes sense during the initial hyperinflammatory phase, immune stimulation by removing inhibitory factors (plasmapheresis) or the administration of monocyte activating cytokines (IFN-gamma, GM-CSF) may be more useful during “immunoparalysis”.

Key words

SepsisPeritonitisMonocyte deactivationIL-10TNF-alphaIFN-gammaGM-CSFPlasmapheresis

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • H. -D. Volk
    • 1
  • P. Reinke
    • 2
  • D. Krausch
    • 3
  • H. Zuckermann
    • 4
  • K. Asadullah
    • 1
  • J. M. Müller
    • 4
  • W. -D. Döcke
    • 1
  • W. J. Kox
    • 3
  1. 1.Institut für Medizinische Immunologie, Universitätsklinikum CharitéHumboldt-Universität zu BerlinBerlinGermany
  2. 2.Medizinische Klinik V-Nephrologie/Transplantation, Universitätsklinikum CharitéHumboldt-Universität zu BerlinBerlinGermany
  3. 3.Klinik für Anaethesiologie und Intensivmedizin, Universitätsklinikum CharitéHumboldt-Universität zu BerlinBerlinGermany
  4. 4.Klinik für Abdominal- und Allgemeinchirurgie, Universitätsklinikum CharitéHumboldt-Universität zu BerlinBerlinGermany