The anti-inflammatory approach to septic shock

Autor: P. Q. Eichacker, C. Natanson
Rok vydání: 1997
Předmět:
Zdroj: Intensivmedizin und Notfallmedizin. 34:101-109
ISSN: 1435-1420
0175-3851
DOI: 10.1007/s003900050026
Popis: Our clinical experience with anti-inflammatory agents in patients with sepsis has been a disappointing one thus far. To better define the role of inflammation and the applicability of immunomodulators in sepsis, we have administered either anti-inflammatory (leukocyte adhesion complex directed monoclonal antibodies, CD11/18 MAb) or pro-inflammatory (recombinant granulocyte colony stimulating factor, G-CSF) agents in animals challenged with infectious or noninfectious inflammatory stimuli at intra- or extravascular sites. Inhibition of inflammation with CD11/18 MAb, reduced lung injury and improved survival with intravenous (TV) tumor necrosis factor (TNF) in canines. However, CD11/18 MAb with intrabronchial (IB) or intraperitoneal (IP) E. coli challenge, although improving lung injury with pneumonia, worsened host defense, hemodynamics and survival. In canines with IP or IB E. coli, or IV endotoxin, prophylactic G-CSF improved host defense, hemodynamics and survival. However, G-CSF with IB E. coli in the canine increased lung dysfunction and with a higher bacterial dose in the rat worsened both lung injury and survival. In additional studies in rats alone, the effects of prophylactic G-CSF on survival were fundamentally different, depending upon the site and the lethality of E. coli challenge. In a final study, canines were challenged with IP E. coli and then treated with G-CSF therapeutically. Despite using a range of doses, G-CSF did not improve any parameter of outcome in these studies and in very high doses appeared harmful. In our animal models, both pro- and anti-inflammatory agents had widely divergent effects on organ injury and survival. The disparate roles of inflammation in host defense and tissue injury may in part explain these results. Altering the inflammatory response during sepsis is more complicated than we originally expected. For pro- and anti-inflammatory agents to be maximally effective in clinical trials of sepsis, our animal data suggest that the influence of variables related to both the therapy (e.g. dose and timing) and the precipitating infection (e.g. severity, site and type) need to be clarified.
Databáze: OpenAIRE
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