Overview of interleukin-18: more than an interferon-gamma inducing factor.
Initially described in 1989 as interferon-gamma (IFN-gamma) inducing factor (IGIF), interleukin-18 (IL-18) is a novel pro-inflammatory cytokine that is clearly more than an inducer of IFN-gamma. The cytokine possesses several biological properties such as activation of nuclear factor-kappaB (NF-kappaB), Fas ligand expression, the induction of both CC and CXC chemokines, and increased production of competent human immunodeficiency virus. Most activities are due to a receptor complex that recruits the IL-1 receptor-activating kinase (IRAK), leading to translocation of NF-kappaB. This property and others support the concept that IL-18 is related to the IL-1 family. Indeed, one of the IL-18 receptor chains is the IL-1 receptor-related protein, a member of the IL-1R family. In addition, IL-18 is structurally similar to IL-1beta and like IL-1beta is first synthesized as a leaderless precursor requiring the IL-1beta converting enzyme for cleavage into an active molecule. The biology of IL-18 is reviewed in the overview and the implication for a role for this cytokine in disease is presented.
Dinarello
C A
CA
University of Colorado Health Sciences Center, Denver 80262, USA.
Novick
D
D
Puren
A J
AJ
Fantuzzi
G
G
Shapiro
L
L
Mühl
H
H
Yoon
D Y
DY
Reznikov
L L
LL
Kim
S H
SH
Rubinstein
M
M
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007369:Interferon Inducers / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D020382:Interleukin-18; D051379:Mice; D051381:Rats
D016207:Cytokines; D007369:Interferon Inducers; D020382:Interleukin-18; D007371:Interferon-gamma