Initial studies on the administration of C1-esterase inhibitor to patients with septic shock or with a vascular leak syndrome induced by interleukin-2 therapy.
Activation of the complement and contact systems occur in patients with septic shock and is associated with a poor outcome. Activation of both systems is regulated by a common inhibitor, C1-esterase inhibitor (C1-Inh). Functional levels of C1-Inh are normal or slightly decreased in septic patients although this inhibitor is an acute phase protein. Moreover, an increased turn-over of C1-Inh in sepsis likely occurs since levels of proteolytically inactivated ("modified") C1-Inh are increased in this syndrome. One may therefore postulate that in sepsis there is a relative deficiency of C1-Inh. Here we will summarize our preliminary studies in 11 patients with septic shock, who received high doses of C1-Inh for up to 5 days. Activation of complement and contact systems also occurs in "a human model for septic shock" i.e., the vascular leak syndrome (VLS) induced by immunotherapy with the cytokine interleukin-2 (IL-2). The similarity between VLS and sepsis is not only reflected by similar patterns of complement and contact activation, but also by comparable hemodynamic and biochemical changes, and by the involvement of a number of other inflammatory mediators, such as the release of pro-inflammatory cytokines, and activation of coagulation and fibrinolysis and of neutrophils. Here we will also summarize our initial studies of the effect of C1-Inh administration to 6 patients with the VLS induced by IL-2. Our results indicate that high doses of C1-Inh can be safely administered to patients with septic shock or with the VLS, and may attenuate complement and contact activation in these conditions. Whether this therapy may reduce mortality and or morbidity of either syndrome has to be established by double-blind controlled studies.
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, University of Amsterdam.
C E
CE
Hack
A C
AC
Ogilvie
B
B
Eisele
P M
PM
Jansen
J
J
Wagstaff
L G
LG
Thijs
D001777:Blood Coagulation / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D003167:Complement Activation / Q000187:drug effects; D003174:Complement C1 Inactivator Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects*; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology; D013329:Structure-Activity Relationship; D013577:Syndrome
D003174:Complement C1 Inactivator Proteins; D007376:Interleukin-2