Centre for Rheumatic Diseases, University of Glasgow, Scotland, United Kingdom
Correspondence: Centre for Rheumatic Diseases, University of Glasgow, 10 Alexandra Parade, Glasgow G31 2ER. E-mail: i.b.mcinnes{at}clinmed.gla.ac.uk
Interleukin-18 (IL-18), a recently described member of the IL-1 cytokine superfamily, is now recognized as an important regulator of innate and acquired immune responses. IL-18 is expressed at sites of chronic inflammation, in autoimmune diseases, in a variety of cancers, and in the context of numerous infectious diseases. This short review will describe the basic biology of IL-18 and thereafter address its potential effector and regulatory role in several human disease states including autoimmunity and infection. IL-18, previously known as interferon-
(IFN-)-inducing factor, was identified as an endotoxin-induced serum factor that stimulated IFN- production by murine splenocytes [1
]. IL-18 was cloned from a murine liver cell cDNA library generated from animals primed with heat-killed Propionibacterium acnes and subsequently challenged with lipopolysaccharide [2
]. Nucleotide sequencing of murine IL-18 predicted a precursor polypeptide of 192 amino acids lacking a conventional signal peptide and a mature protein of 157 amino acids. Subsequent cloning of human IL-18 cDNA revealed 65% homology with murine IL-18 [3
] and showed that both contain an unusual leader sequence consisting of 35 amino acids at their N terminus.
Key Words: cytokine • inflammation • autoimmunity • infectious disease • interleukin-18
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
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|
|
|
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|
|
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|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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