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IL18

IL-18, also known as interferon-gamma-inducing factor, is a proinflammatory cytokine of the interleukin-1 family. It is produced as an inactive precursor (pro-IL-18) by several cell types, including monocytes, macrophages, dendritic cells, and epithelial cells. Activation requires proteolytic cleavage by caspase-1 within the inflammasome, yielding mature IL-18 that is secreted to act in an autocrine, paracrine, and endocrine manner.

IL-18 signals through a heterodimeric receptor complex composed of IL-18Rα and IL-18Rβ on target cells. The receptor

IL-18 activity is regulated by IL-18 binding protein (IL-18BP), a natural decoy receptor that neutralizes free

engages
the
adaptor
protein
MyD88,
leading
to
downstream
activation
of
NF-κB
and
MAP
kinases
and
the
production
of
inflammatory
mediators.
Biological
effects
of
IL-18
include
induction
of
interferon-gamma
production
by
natural
killer
cells
and
T
cells,
especially
in
synergy
with
IL-12,
thereby
promoting
Th1-type
cellular
immunity.
It
also
promotes
the
expression
of
chemokines
and
other
proinflammatory
cytokines
and
can
influence
macrophage
activation
and
cytotoxic
function.
The
outcome
is
context
dependent
and
can
range
from
protective
roles
in
infection
to
contribution
to
chronic
inflammation.
IL-18.
Dysregulation
of
IL-18
signaling
has
been
observed
in
inflammatory
and
autoimmune
diseases,
sepsis,
macrophage
activation
syndrome,
and
in
some
cancers,
where
elevated
IL-18
levels
may
relate
to
disease
activity
or
prognosis.
Therapeutic
approaches
to
inhibit
IL-18
signaling,
including
IL-18BP
and
neutralizing
antibodies,
are
under
investigation
for
IL-18–mediated
diseases.