Document Detail


A novel selective extracorporeal intervention in sepsis: immunoadsorption of endotoxin, interleukin 6, and complement-activating product 5a.
MedLine Citation:
PMID:  17558345     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In sepsis, endotoxin, interleukin 6 (IL-6), and complement-activation product 5a (C5a) trigger inflammatory cascades resulting in monocytic deactivation. When this occurs, the outcome is often uncontrolled infection, multiple organ dysfunction, and death. We tested here whether simultaneous reduction of systemic endotoxin, IL-6, and C5a levels could be achieved via selective extracorporeal immunoadsorption (IA) and whether this would restore monocytic responsiveness and improve organ function. Therefore, 33 patients with severe sepsis or septic shock were enrolled in a prospective, 1:2 case-control matched, blinded endpoint evaluation trial. In addition to best supportive care, 11 of these patients (mean age, 57.8 +/- 2.2 years; Acute Physiology and Chronic Health Evaluation II score, 23.7 +/- 1.6) received simultaneous endotoxin IA, IL-6 IA, and C5a IA on 5 consecutive days for 7.5 h each. Our observational end points were the course of monocytic immunity (monocytic HLA-DR expression) and other indices of inflammation and disease severity. In patients receiving IA, the mean circulating level of IL-6 was reduced from 361.7 +/- 116.0 to 38.2 +/- 15.2 pg/mL (P = 0.02), and of C5a from 297.6 +/- 43.1 to 79.2 +/- 14.5 ng/mL (P < 0.001). Two indices of endotoxemia were reduced also. Treated patients had lower C-reactive protein and Acute Physiology and Chronic Health Evaluation II scores at day 7 (P = 0.004 and P = 0.0001, respectively). Monocytic HLA-DR improved in the treated patients but not in controls (P < 0.0001). Under treatment, HLA-DR was found to recover in all patients with immunoparalysis (4,993.6 +/- 1,162 to 15,295.3 +/- 2,197 molecules per cell; P = 0.002). Here, we demonstrate that simultaneously reducing circulating endotoxin, IL-6, and C5a levels by selective IA reverses monocytic deactivation and improves organ system functions. This novel strategy might open a new therapeutic avenue for an interventional extracorporeal treatment of patients with sepsis.
Authors:
Joerg C Schefold; Stephan von Haehling; Malte Corsepius; Cosima Pohle; Peter Kruschke; Heidrun Zuckermann; Hans-Dieter Volk; Petra Reinke
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  28     ISSN:  1073-2322     ISO Abbreviation:  Shock     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-12     Completed Date:  2008-01-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  418-25     Citation Subset:  IM    
Affiliation:
Department of Nephrology and Intensive Care Medicine, University Medicine Berlin, Charité Campus Virchow Clinic, Berlin, Germany.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00146432
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Case-Control Studies
Complement C5a / metabolism*
Endotoxins / blood*
Enzyme-Linked Immunosorbent Assay
Extracorporeal Circulation / methods*
Female
Follow-Up Studies
Humans
Immunity, Cellular / immunology
Inflammation / blood,  pathology,  therapy
Interleukin-6 / blood*
Male
Middle Aged
Monocytes / metabolism
Prospective Studies
Sepsis / blood,  pathology,  therapy*
Chemical
Reg. No./Substance:
0/Endotoxins; 0/Interleukin-6; 80295-54-1/Complement C5a

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