A novel IL-18BP ELISA shows elevated serum IL-18BP in sepsis and extensive decrease of free IL-18

Cytokine. 2001 Jun 21;14(6):334-42. doi: 10.1006/cyto.2001.0914.


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 ( approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Antibodies, Monoclonal / metabolism
  • Binding Sites
  • COS Cells
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay / methods*
  • Glutathione Transferase / metabolism
  • Glycoproteins / blood*
  • Glycoproteins / urine
  • Humans
  • Hybridomas / metabolism
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-18 / blood*
  • Kinetics
  • Ligands
  • Mice
  • Protein Isoforms
  • Radioimmunoassay
  • Recombinant Fusion Proteins / metabolism
  • Sepsis / blood*


  • Antibodies, Monoclonal
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-18
  • Ligands
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • interleukin-18 binding protein
  • Glutathione Transferase