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A NOVEL IL-18BP ELISA SHOWS ELEVATED SERUM IL-18BP IN SEPSIS AND EXTENSIVE DECREASE OF FREE IL-18

2001; Elsevier BV; Volume: 14; Issue: 6 Linguagem: Inglês

10.1006/cyto.2001.0914

1096-0023

Daniela Novick, Boris Schwartsburd, Ron Pinkus, Dan Suissa, Ilana Belzer, Zev Sthoeger, W. F. Keane, Yolande Chvatchko, Soo Hyun Kim, Giamila Fantuzzi, Charles A. Dinarello, Menachem Rubinstein,

Cell death mechanisms and regulation

IL-18 binding protein (IL-18BP) is a circulating antagonist of the proinflammatory Th1 cytokine IL-18. It effectively blocks IL-18 by forming a 1:1 high affinity (Kd=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 determined. Using this ELISA, we measured serum IL-18BPa in large cohorts of healthy individuals and in septic patients. Serum IL-18BPa in healthy individuals 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 same 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 (∼85%) was in its free form. Total 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, most 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 considerably inhibits circulating IL-18 in sepsis. Yet, exogenous administration of IL-18BPa may further reduce circulating IL-18 activity.