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Clinical and Diagnostic Laboratory Immunology, July 2003, p. 529-535, Vol. 10, No. 4
1071-412X/03/$08.00+0     DOI: 10.1128/CDLI.10.4.529-535.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Administration of C1 Inhibitor Reduces Neutrophil Activation in Patients with Sepsis

Sacha Zeerleder,1,2,3 Christoph Caliezi,1 Gerard van Mierlo,2 Anke Eerenberg-Belmer,2 Irmela Sulzer,1 C. Erik Hack,2,4 and Walter A. Wuillemin3*

Central Hematology Laboratory, Inselspital, Bern,1 Division of Hematology, Department of Internal Medicine, Kantonsspital, Lucerne, Switzerland,3 Sanquin Research at the CLB,2 Department of Clinical Chemistry, Vrije Universiteit Medical Center, Amsterdam, The Netherlands4

Received 19 September 2002/ Returned for modification 22 January 2003/ Accepted 8 April 2003

Forty patients with severe sepsis or septic shock recently received C1 inhibitor. In the present study we studied the effect of C1 inhibitor therapy on circulating elastase-{alpha}1-antitrypsin complex (EA) and lactoferrin (LF) levels in these patients to gain further insight about agonists involved in the activation of neutrophils in human sepsis. Elevated levels of EA and LF were found in 65 and 85% of the septic patients, respectively. Patients with elevated EA levels had higher organ dysfunction scores, higher levels of cytokines, and higher levels of complement activation products than patients with normal EA levels. C1 inhibitor therapy reduced EA as well as complement activation and IL-8 release in the patients with elevated EA on admission. We conclude that neutrophil activation in human sepsis correlates with the severity of organ dysfunction and involves complement and interleukin-8 as agonists. The effect of C1 inhibitor therapy on neutrophils may provide an explanation for the beneficial, although mild, effects of this treatment on organ dysfunction in sepsis.

* Corresponding author. Mailing address: Division of Hematology, Department of Internal Medicine, Kantonsspital, 6000 Lucerne-16, Switzerland. Phone: 41 41 205 51 47. Fax: 41 41 205 21 97. E-mail: walter.wuillemin{at}ksl.ch.

Clinical and Diagnostic Laboratory Immunology, July 2003, p. 529-535, Vol. 10, No. 4
1071-412X/03/$08.00+0     DOI: 10.1128/CDLI.10.4.529-535.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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