Cytokines: Interleukins
143
4.18
Interleukin-18
IL-18, formerly known as
interferon gamma
inducing factor
(
IGIF
) and now known
to be structurally related to IL-1, appears
to be mainly involved in the augmenta-
tion of Th1 cellular immune responses
to
invading
pathogens.
Its
capacity
to
induce IFN
γ
is reliant on the costimu-
lation of T lymphocytes by IL-12, whose
synthesis is induced by bacterial LPS in
monocytes/macrophages. It has also been
shown to enhance Fas ligand-mediated
cytotoxicity of cloned murine Th1 cells,
but not Th0 or Th2 cells. Its activities are
mediated by IL-1 receptor-related protein
(IL-1Rrp), an Ig superfamily member re-
lated to IL-1RI, and can be inhibited by a
naturally occurring, speci±c IL-18 binding
protein.
4.19
Interleukin-19
IL-19, one of several IL-10 paralogs, is
produced mainly by LPS-stimulated mono-
cytes and macrophages and in common
with IL-10 is expected to exert immunoreg-
ulatory functions that influence the ac-
tivities
of
many
of
the
cell
types
in
the
immune
system.
It
appears
prob-
able that IL-19 will, like IL-10, act as
a feedback inhibitor of proinflammatory
cytokine, for example, IL-1, TNF
α
synthe-
sis and thus initiate immunosuppressive
effects.
4.20
Interleukin-20
IL-20, one of several IL-10 paralogs, is
in contrast to IL-10 and IL-19 produced
mainly by skin cells, and is thus expected
to target distinctive activities on typical
skin cells such as keratinocytes, which ex-
press its speci±c heterodimeric receptor,
IL-20R1/IL-20R2. Overexpression of IL-20
has been shown to result in severe skin
abnormalities, including hyperkeratosis,
hyperproliferation, and aberrant epider-
mal differentiation.
4.21
Interleukin-21
IL-21, which is most closely related to
IL-15, is one of the several structurally
related cytokines, including IL-2, which
is secreted by
activated CD4
+
T cells
as part of the normal response to for-
eign
antigens.
Its
main
role
appears
to
be
as
a
differentiation
factor
for
NK
cells.
It
has
been
shown
to
pro-
mote IFN
γ
synthesis, which acts to en-
hance macrophage killing of microbial
pathogens, and to prevent apoptosis of
precursor NK cells, allowing them to be-
come terminally differentiated and fully
activated.
4.22
Interleukin-22
IL-22,
one
of
several
IL-10
paralogs,
formerly known as IL-10-related T
-cell-
derived i
nducible f
actor (IL-TIF) is pri-
marily produced by activated CD4
+
T
cells, but unlike immunoregulatory IL-
10, its target cell types include mesangial,
neuronal, and liver cells (hepatocyctes).
Its action on hepatocytes (and hepatoma
cell lines) appears similar to that of IL-
6 in that it results in the upregulation
of a number of acute-phase proteins. It
should
therefore
probably
be
included
with other proinflammatory cytokines as
a
prime
mediator
of
the
acute-phase
response.
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