IL-18 binding protein (IL-18BP) is a circulating antagonist of the proinfla
mmatory Th1 cytokine IL-18. It effectively blocks IL-18 ky forming a 1:1 hi
gh affinity (K-d=400 pM) complex, exhibiting a very low dissociation rate.
We have developed a sandwich ELISA for IL-18BPa and determined its limit of
detection (62 pg/ml). Interference by IL-18 and related cytokines, as well
as cross reactivity with other IL-18BP isoforms (b, c, and d) were determi
ned. Using this ELISA, we measured serum IL-18BPa in large cohorts of healt
hy individuals and in septic patients. Serum IL-18BPa in healthy individual
s was 2.15 +/- 0.15 ng/ml (range 0.5-7 ng/ml). In sepsis, the level rose to
21.9 +/- 1.44 ng/ml (range 4-132 ng/ml). Total IL-18 was measured in the s
ame sera by an electrochemiluminescence assay and free IL-18 was calculated
based on the mass action law. Total IL-18 was low in healthy individuals (
64 +/- 17 pg/ml) and most of it (similar to 85%) was in its free form. Tota
l IL-18 and IL-18BPa were both elevated in sepsis patients upon admission (
1.5 +/- 0.4 ng/ml and 28.6 +/- 4.5 ng/ml, respectively). At these levels, m
ost of the IL-18 is bound to IL-18BPa, however the remaining free IL-18 is
still higher than in healthy individuals. We conclude that IL-18BPa conside
rably inhibits circulating IL-18 in sepsis. Yet, exogenous administration o
f IL-18BPa may further reduce circulating IL-18 activity.
(C) 2001 Academic Press.