title: A novel selective extracorporeal intervention in sepsis: immunoadsorption of endotoxin, interleukin 6, and complement-activating product 5a.
abstract: 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.affiliation: Department of Nephrology and Intensive Care Medicine, University Medicine Berlin, Charité Campus Virchow Clinic, Berlin, Germany.
authors.forename: Joerg C
authors.initials: JC
authors.lastname: Schefold
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.forename: Malte
authors.initials: M
authors.lastname: Corsepius
authors.forename: Cosima
authors.initials: C
authors.lastname: Pohle
authors.forename: Peter
authors.initials: P
authors.lastname: Kruschke
authors.forename: Heidrun
authors.initials: H
authors.lastname: Zuckermann
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
mesh_terms: D000704:Analysis of Variance; D016022:Case-Control Studies; D015936:Complement C5a / Q000378:metabolism*; D004731:Endotoxins / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005112:Extracorporeal Circulation / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007249:Inflammation / Q000097:blood / Q000473:pathology / Q000628:therapy; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood / Q000473:pathology / Q000628:therapy*
chemical_list: D004731:Endotoxins; D015850:Interleukin-6; D015936:Complement C5a