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An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions

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Interleukin-18 and IL-18 binding protein.

Charles A Dinarello¹, Daniela Novick, Soohyun Kim

¹Department of Medicine, University of Colorado Denver , Aurora, CO , USA ; Department of Medicine, University Medical Center Nijmegen , Nijmegen , Netherlands.

Frontiers in Immunology

|October 12, 2013

Summary

Interleukin-18 (IL-18) is a cytokine involved in inflammation. An imbalance between IL-18 and its binding protein (IL-18BP) is linked to disease severity, with therapeutic strategies now in clinical trials.

Keywords:

autoimmune diseases inflammasomes inflammation interleukin-1 macrophages

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Area of Science:

Immunology
Cytokine Biology

Background:

Interleukin-18 (IL-18) is an IL-1 family cytokine synthesized as an inactive precursor, processed by caspase-1.
Unlike IL-1β, the IL-18 precursor is constitutively present in most cells.
IL-18 activity is regulated by the naturally occurring IL-18 binding protein (IL-18BP).

Purpose of the Study:

To review the biology of Interleukin-18 (IL-18).
To update on the role of IL-18 in various human diseases.
To discuss the therapeutic potential of IL-18BP and anti-IL-18 antibodies.

Main Methods:

Literature review of studies on IL-18 and IL-18BP.
Analysis of animal models using IL-18BP, IL-18-deficient mice, IL-18 neutralization, or IL-18 receptor alpha chain deficiency.
Examination of clinical trial data for IL-18BP and anti-IL-18 antibodies.

Main Results:

Elevated free IL-18 levels, due to IL-18/IL-18BP imbalance, correlate with increased disease severity in humans.
IL-18 plays a significant role in interferon-γ production by T-cells and natural killer cells.
IL-18 involvement is noted in autoimmune diseases, myocardial function, emphysema, metabolic syndromes, psoriasis, inflammatory bowel disease, hemophagocytic syndromes, macrophage activation syndrome, sepsis, and acute kidney injury, with protective roles observed in some models.

Conclusions:

IL-18BP has demonstrated safety in human use.
Clinical trials are underway for both IL-18BP and neutralizing anti-IL-18 antibodies.
Understanding IL-18 biology and its role in disease is crucial for developing targeted therapies.