Cytokines: Interleukins
145
chain designated IL-28R
α
.IL
-28induces
interferon-stimulated response elements
(ISRE), but not via IFN receptors, and
mediates moderate antiviral activity in re-
sponse to virus infection. This has led to
IL-28A and B being also named as IFNs,
IFN-lambda2, and -lambda3, respectively.
In common with IFNs, IL-28 upregulates
several known IFN-responsive genes, in-
cluding MxA, 2-5A synthetase, and class I
MHC antigen.
4.29
Interleukin-29
IL-29 shows 81% sequence homology to
IL-28 and acts in a very similar way. It also
has been shown to induce IFN-responsive
genes and exert antiviral activity, and thus
is alternatively designated IFN-lambda1.
5
Interleukin Physiology
Interleukins are mainly, but not exclu-
sively, inducible mediators of nonspeci±c
host resistance and adaptive immunity,
that
is,
they
are
stimulators
of
host-
protective mechanisms against infectious
and invasive diseases. The biological ef-
f
e
c
t
so
fm
o
s
ti
n
t
e
r
l
e
u
k
i
n
sa
r
er
e
a
d
i
l
y
observable
in vivo
. However, the adminis-
tration of high doses of a single interleukin
by abnormal routes may also create im-
balances that perturb homeostatic mecha-
nisms resulting in aberrant biological and
physiological responses. Therefore, stud-
ies in which de±ciencies of interleukin
production or action can be investigated
can provide perhaps a better guide to
the physiological role(s) of individual in-
terleukins. Such studies can either be
done by blocking interleukin action, for
example, with anti-interleukin antibodies,
antireceptor antibodies, or soluble recep-
tors, or by examining the effects of genetic
de±ciencies in interleukin protein or re-
ceptor. The former are probably the less
satisfactory of the two approaches since
interleukin production needs to be stim-
ulated before an effect of an inhibitor of
interleukin action can be demonstrated.
Generally speaking, it is not possible to in-
duce the production of a single interleukin;
several interleukins and cytokines are nor-
mally produced in response to a stimulant.
In addition, most antibodies used will be
foreign (xenogenic) to the responding ani-
mal, and this may result in problems of an
immunological nature.
There have been very few natural ge-
netic de±ciencies in interleukin genes and
interleukin-receptor genes identi±ed so
far. However, it is now possible to arti-
±cially create knockout mutations in mice
by using the strategy of gene targeting
in embryonic stem (ES) cells. Increasing
numbers of different knockout mice are
being created, and it is perhaps surprising
that some of them apparently develop nor-
mally, are born alive, and can grow and
survive for weeks, if not months. Possibly,
compensatory molecules or mechanisms
are induced in these knockout mice. In the
IL-2 knockout or null mouse, for exam-
ple, development is normal with no effects
being observed on the early development
of thymocytes and inactivation of T lym-
phocytes within the thymus. However, a
lack of response of mature T cells to poly-
clonal activators together with a lack of T
cell–mediated ‘‘help’’, that is, interleukin
production, for B-cell growth and differen-
tiation were manifest in these mice. There
were also excessively high levels of IgG1
and IgE found. About half of these mice be-
came severely immunocompromised and
died between four and nine weeks from
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