Administration of C1 inhibitor reduces neutrophil activation in patients with sepsis.
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.
Zeerleder
Sacha
S
Central Hematology Laboratory, Inselspital, Bern, Switzerland.
Caliezi
Christoph
C
van Mierlo
Gerard
G
Eerenberg-Belmer
Anke
A
Sulzer
Irmela
I
Hack
C Erik
CE
Wuillemin
Walter A
WA
D000328:Adult; D000368:Aged; D015415:Biomarkers; D003167:Complement Activation / Q000187:drug effects; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007781:Lactoferrin / Q000097:blood; D019272:Leukocyte Elastase / Q000097:blood; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015843:Serpins / Q000494:pharmacology / Q000627:therapeutic use*; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy; D000515:alpha 1-Antitrypsin
D015415:Biomarkers; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D016207:Cytokines; D016209:Interleukin-8; C469952:SERPING1 protein, human; D015843:Serpins; D000515:alpha 1-Antitrypsin; C037741:alpha 1-antitrypsin-leukocyte elastase complex; D007781:Lactoferrin; D019272:Leukocyte Elastase