Skip to main content

Immunoadsorption of lipopolysaccharides, IL-6 and complement-activation product 5a in severe sepsis and septic shock

Background

In severe sepsis and septic shock, endotoxin (lipopolysaccharides [LPS]), IL-6 and complement-activation product 5a (C5a) trigger inflammatory cascades resulting in multiple organ dysfunction and failure of the cell-mediated immune system (immunoparalysis). This correlates with uncontrolled infection and fatal outcome. We therefore determined whether simultaneous removal of systemic LPS, IL-6 and C5a by selective immunoadsorption (IA) reduces hyperinflammation, reverses immunoparalysis and improves organ functions in patients with severe sepsis and septic shock.

Design

In a prospective, controlled, open-label fashion, 29 patients with severe sepsis or septic shock hospitalized in the ICUs of a university hospital were included in a proof-of-concept trial (ISASS-1). Patients were enrolled between 2002 and 2004 and followed-up for 28 days, until hospital discharge or death.

Methods

In addition to the best supportive ICU care, 11 patients (age 57.8 ± 2.2 years, Acute Physiology and Chronic Health Evaluation II [APACHE-II] score 23.7 ± 1.6) received extra-corporeal LPS-IA, IL-6-IA and C5a-IA on 5 consecutive days for 7.5 hours each. As control, prognostically relevant parameters of 18 contemporary patients (age 55.2 ± 2.6, APACHE II score 22.9 ± 1.2) were followed up.

Results

There was no difference between the study groups at baseline. Target molecules were reduced under IA: IL-6 (361.7 ± 116.0 to 38.2 ± 15.2 pg/ml, P = 0.003), C5a (297.6 ± 43.1 to 79.2 ± 14.5 ng/ml, P < 0.001) and markers of endotoxemia. In IA-treated individuals, IL-6 (P < 0.001), CRP (P = 0.001) and APACHE II score (P = 0.002) was significantly lower at day 7. Monocytic HLA-DR improved in IA patients (P < 0.001) and was unchanged in controls. HLA-DR recovered in all immunoparalytic patients under IA (4993.6 ± 1162 to 15,295.3 ± 2197 molecules/ cell, P = 0.002).

Conclusion

Immunoadsorption is a new, selective approach to target key inflammatory mediators in septic patients. Simultaneous targeting of LPS, IL-6 and C5a reduced major inflammatory mediators, reversed immunoparalysis and improved major disease severity scores.

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Schefold, J., Corsepius, M., Pohle, C. et al. Immunoadsorption of lipopolysaccharides, IL-6 and complement-activation product 5a in severe sepsis and septic shock. Crit Care 10, P288 (2006). https://doi.org/10.1186/cc4635

Download citation

Keywords

  • Septic Shock
  • Severe Sepsis
  • Inflammatory Mediator
  • Septic Patient
  • Inflammatory Cascade