Cytokines: Interleukins
135
increasing
pituitary
adrenocorticotropic
hormone (ACTH) and endorphin levels
as well as glucocorticoids. Administration
of
IL-1
causes
neutrophilia,
probably
due to IL-1-mediated induction of GM-
CSF from endothelial cells. The latter
are activated and sticky for lymphocytes
and monocytes due to increased ICAM-
1 expression. There are effects on liver
function leading to increased amino acid
turnover and hyperlipidemia. By itself, but
particularly in combination with TNF
α
and/or bacterial LPS, high levels of IL-1 can
lead to profound hypotension, myocardial
suppression, shock, and death.
The biological activities of IL-1 and other
interleukins are summarized in Table 5.
4.2
Interleukin-2
In contrast to IL-1, IL-2 is much more lim-
ited in its biological activities, due largely
to the restricted expression of high-af±nity
IL-2 receptors to a relatively few cell types.
Mitogen- or antigen-activated mature T
lymphocytes express high-af±nity IL-2R
and subsequent interaction with IL-2 leads
to clonal proliferation. Many T-cell lines
and clones, speci±c for particular antigens,
remain wholly or partially dependent on
the presence of exogenous IL-2 for prolif-
eration. In addition, antigen-independent
murine cytotoxic T-lymphocyte line (CTLL)
requires IL-2 for continuous growth. NK
cells, contained within the large granular
lymphocyte (LGL) population, express IL-
2Rß and not only proliferate in response
to IL-2 but also exhibit enhanced cytolytic
activity.
In
the
presence
of
high
IL-2
concentrations, the so-called lymphokine-
activated killer (LAK) cells emerge from
resting populations of lymphoid cells. LAK
cells, which are cytolytic for some tumor
cells, can be induced
in vitro
and
in vivo
.
IL-2 can also act on activated B lympho-
cytes to stimulate both their proliferation
and the induction of Ig synthesis.
Besides its growth-promoting activity,
IL-2
stimulates
T
cells
to
secrete
a
range of other interleukins and cytokines
(Table 3).
While
the
principal
role
of
these
interleukins
and
cytokines
is
to
act as ‘‘helper factors’’ for the growth
and
differentiation
of
leucocytes
other
than T lymphocytes, they could also be
involved in the differentiation of the latter.
Thus,
IL-2
may
indirectly
regulate
T-
lymphocyte differentiation, for example, in
the maturation of CTL or LAK to express
cytolytic activity.
In vivo
, IL-2 induces lymphoid hyper-
plasia, for example, increases in mature
T cells, neutrophilia, and eosinophilia;
the latter are probably indirectly caused
by IL-2 induced interleukin/cytokine syn-
thesis
by
activated
T
cells.
LAK
cells
appear rapidly following the infusion of
IL-2. However, high doses of IL-2 induce
undesirable side effects such as hypoten-
sion, oliguria, fluid retention, progressive
dyspnoea (dif±culty in breathing), atrial
arrhythmias, thrombocytopenia, and vas-
cular leak syndrome.
4.3
Interleukin-3
IL-3 has been called the pan-speci±c inter-
leukin because of its highly pleiotropic
activities.
Like
IL-2,
IL-3
acts
mainly
as
a
speci±c
growth
factor,
princi-
pally
affecting
the
proliferation
and
differentiation of erythroid and myeloid
lineages.
It
has
been
shown
to
be
particularly effective in stimulating the
proliferation of early
erythroid/myeloid
progenitors, for example, in the forma-
tion of granulocyte-erythroid-macrophage-
megakaryocyte
colony-forming
units
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