Interleukin 18 (IL
-
18) is a
n
18
kDa
cytokine which identified as a c
ostimulatory factor for
production of interferon
-
?
(IFN
-
?
) in response to toxic
shock and shares functional similarities with IL
-
12. IL
-
18
is
synthesized as a precursor 24 kDa molecule without a
signal
peptide and must be cleaved to produce an active
molec
ule.
IL
-
1 converting enzyme (ICE, Caspase
-
1)
cleaves pro
-
IL
-
18
at aspartic acid in the P1 position,
producing the mature,
bioactive peptide that is readily
released from the cells. It is
reported that IL
-
18 is produced
from Kupffer cells,
activated macroph
ages, keratinocytes,
intestinal epithelial
cells,
osteoblasts, adrenal cortex cells
and murine
diencephalon.
IFN
-
?
is produced by activated T
or NK cells and plays critical roles in the defense against
microbiral pathogens.
IFN
-
?
activates macrophages,
enhances NK activity and B
cell maturation, proliferation
and Ig secretion, induces MHC
class I and II antigens, and
inhibits osteoclast activation.
IL
-
18 acts on T helper
type
-
1
(Th1)
T cells and in combination
with IL
-
12 strongly
induces them to produce IFN
-
?
.
Pleiotropic effects of IL
-
18
has also been reported, such as,
enhancement production of
IFN
-
?
and GM
-
CSF in
p
eripheral blood mononuclear cells,
production of Th1 cytokines, IL
-
2, GM
-
CSF and IFN
-
?
in
T cells,
enhancement of Fas ligand expression by Th1 cells.