Acute removal of common sepsis mediators does not explain the effects of extracorporeal blood purification in experimental sepsis

Zhi-Yong Peng^1,4, Hong-Zhi Wang^1,2,4, Melinda J Carter¹, Morgan V Dileo³, Jeffery V Bishop¹, Fei-Hu Zhou¹, Xiao-Yan Wen¹, Thomas Rimmelé¹, Kai Singbartl¹, William J Federspiel^1,3, Gilles Clermont^1,3 and John A Kellum^1,

1. ¹The CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute illness) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
2. ²Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Intensive Care Unit, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China
3. ³McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

Kidney International (2012) 81, 363–369; doi:10.1038/ki.2011.320; published online 14 September 2011

http://www.nature.com/ki/journal/v81/n4/abs/ki2011320a.html

Abstract

The effect of extracorporeal blood purification on clinical outcomes in sepsis is assumed to be related to modulation of plasma cytokine concentrations. To test this hypothesis directly, we treated rats that had a cecal ligation followed by puncture (a standard model of sepsis) with a modest dose of extracorporeal blood purification that did not result in acute changes in a panel of common cytokines associated with inflammation (TNF-α, IL-1β, IL-6, and IL-10). 

Pre- and immediate post-treatment levels of these cytokines were unchanged compared to the sham therapy of extracorporeal circulation without blood purifying sorbent. The overall survival to 7 days, however, was significantly better in animals that received extracorporeal blood purification compared to those with a sham procedure. This panel of common plasma cytokines along with alanine aminotransferase and creatinine was significantly lower 72 h following extracorporeal blood purification compared to sham-treated rats. Thus, the effects of this procedure on organ function and survival do not appear to be due solely to immediate changes in the usual measured circulating cytokines. 

These results may have important implications for the design and conduct of future trials in sepsis including defining alternative targets for extracorporeal blood purification and other therapies