Cytokines: Interleukins
141
can be considered as an anti-inflammatory
agent. In contrast, IL-10 enhances B-cell
proliferation and Ig synthesis.
Th1 cells are generally host-protective
for several infectious diseases. Therefore,
the suppression of Th1 cell activities will
favor the growth of the infecting agent. In
this context, it is interesting that EBV and
several other large DNA viruses encode
(viral) IL-10 molecules with limited homol-
ogy to IL-10, but which act through IL-10R
and thus have the same activities as IL-10.
These viral IL-10 homologs appear to in-
duce immunosuppression, thus providing
an immune-evasion mechanism for such
viruses. In contrast, the paralogous IL-10-
related proteins, IL-19, -20, -22, -24 -26, -28,
and -29 with similar limited homology to
IL-10, act through distinct heterodimeric
receptors composed of receptor chains be-
longing to the type II cytokine receptor
family, which also includes receptors for
interferons.
4.11
Interleukin-11
IL-11, produced by bone marrow–derived
stromal cells, appears to be intimately in-
volved in hematopoiesis and, in particular,
the generation of megakaryocytes.
In vitro
studies suggest that IL-11 is capable of di-
rectly supporting the proliferation of com-
mitted murine myeloid progenitors and,
like IL-6 and G-CSF, acts synergistically
with IL-3 to shorten the Go phase of the
cell cycle in early progenitors. Although IL-
11 has no inherent megakaryocytic colony
stimulating activity, it can synergize with
IL-3 in stimulating human and murine
megakaryocyte colony formation.
In many respects, the activities of IL-
11 are very similar to those of IL-6. For
example, like IL-6, IL-11 has been found to
promote an increase in the number of Ig-
secreting B cells. It has also been shown
to stimulate the proliferation of an IL-6-
dependent murine plasmacytoma cell line,
and to act as an autocrine growth factor for
human megakaryoblastic cell lines. Lastly,
IL-11 appears to stimulate the synthesis
of hepatic acute-phase proteins, but is less
effective than IL-6.
4.12
Interleukin-12
The actions of IL-12 are primarily on T
cells and NK cells. It appears to be a
necessary factor in the generation of Th1
lymphocytes from naive or uncommitted
Tc
e
l
l
s
.I
na
d
d
i
t
i
o
n
,t
h
e
r
ea
r
er
e
s
u
l
t
s
that indicate that IL-12 stimulates IFN
γ
production by T cells and NK cells by
cooperation with either IL-1, or IL-18,
or TNF
α
. The presence of IFN
γ
may
also favor the development of the Th1
subset by inhibiting the production of IL-
10 by macrophages. IL-12 appears to be
an important factor for the differentiation
and maturation of dendritic cells.
The
emerging
experimental
data
for
IL-12 therefore strongly suggest that it
plays
an
important
part
in
the
initia-
tion of immune responses by providing
a
link between natural
resistance me-
diated by phagocytic cells, for example,
macrophages, and NK cells and adaptive
immunity mediated by Th cells, CTL, and
B cells. In support of this proposed role, re-
combinant IL-12 has recently been shown
to cure mice infected with the parasite,
Leishmania major. A neutralizing anti-
body against IFN
γ
abrogated the curative
effect of IL-12 indicating that IL-12 was
acting by stimulating T-cell and/or NK-cell
IFN
γ
-production
in vivo
, and the devel-
opment of a protective Th1-cell immune
response. Conversely, generation of Th2
cells and associated immune responses
was inhibited.
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