C1-esterase inhibitor attenuates the inflammatory response during human endotoxemia.

Summary of "C1-esterase inhibitor attenuates the inflammatory response during human endotoxemia."

OBJECTIVE:
: Besides its role in regulation of the complement and contact system, C1-esterase inhibitor has other immunomodulating effects that could prove beneficial in patients with acute inflammation such as during sepsis or after trauma. We examined the immunomodulating properties of C1-esterase inhibitor during human experimental endotoxemia, in which the innate immune system is activated in the absence of activation of the classic complement pathway.
DESIGN:
: Double-blind placebo-controlled study.
SETTING:
: Research intensive care unit of the Radboud University Nijmegen Medical Centre.
SUBJECTS:
: Twenty healthy volunteers.
INTERVENTIONS:
: Intravenous injection of 2 ng/kg Escherichia coli lipopolysaccharide. Thirty minutes thereafter (to prevent binding of lipopolysaccharide), C1-esterase inhibitor concentrate (100 U/kg, n = 10) or placebo (n = 10) was infused. MEASUREMENTS AND MAIN
RESULTS:
: Pro- and anti-inflammatory mediators, markers of endothelial and complement activation, hemodynamics, body temperature, and symptoms were measured. C1-esterase inhibitor reduced the release of proinflammatory cytokines as well as C-reactive protein (peak levels of: interleukin-6 1521 +/- 209 vs. 932 +/- 174 pg/mL [p = .04], tumor necrosis factor-alpha 1213 +/- 187 vs. 827 +/- 167 pg/mL [p = .10], monocyte chemotactic protein-1 6161 +/- 1302 vs. 3373 +/- 228 pg/mL [p = .03], interleukin-1beta 34 +/- 5 vs. 23 +/- 2 pg/mL [p < .01], C-reactive protein 39 +/- 4 vs. 29 +/- 2 mg/L [p = .02]). In contrast, release of the anti-inflammatory cytokine interleukin-10 was increased by C1-esterase inhibitor (peak level 73 +/- 11 vs. 121 +/- 18 pg/mL, p = .02). The increase in interleukin-1 receptor antagonist tended to be smaller in the C1-esterase inhibitor group, but this effect did not reach statistical significance (p = .07). Markers for endothelial activation were increased after lipopolysaccharide infusion, but no significant differences between groups were observed. The lipopolysaccharide-induced changes in heart rate, blood pressure, body temperature, and symptoms (all p < .001 over time) were not influenced by C1-esterase inhibitor. Complement fragment C4 was not increased after lipopolysaccharide challenge.
CONCLUSIONS:
: This study is the first to demonstrate that C1-esterase inhibitor exerts anti-inflammatory effects in the absence of classic complement activation in humans.

Affiliation

From the Department of Intensive Care Medicine (MJD, LAEC, MPB, JGvdH, PP), Radboud University Nijmegen Medical Centre, The Netherlands; the Departments of Surgery (TV, LPHL) and Respiratory Medicine (JP, LK), University Medical Centre Utrecht, The Nether

Journal Details

This article was published in the following journal.

Name: Critical care medicine
ISSN: 1530-0293
Pages:

Links

• PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20693886
• DOI: http://dx.doi.org/10.1097/CCM.0b013e3181f17be4