Cytokines: Interleukins
119
bacteria. Since then and particularly in the
late 1960s and early 1970s, many other bi-
ological activities have been defned, being
originally ascribed to poorly characterized,
soluble Factors. Thus, lymphocyte activat-
ing Factor (LA±) was the name given by
immunologists to a macrophage-derived
substance that enhanced mitogen-driven
lymphocyte proliFeration. A substance se-
creted
by
such
mitogen
(lectin)-driven
lymphocytes was shown to specifcally sup-
port the proliFeration oF T lymphocytes and
was thereFore named
T-cell growth factor
(
TCGF
). Subsequently, a number oF other
growth and diFFerentiation Factors acting
on specifc cell lineages were described.
By the late 1970s, it was beginning to be
realized that some oF these soluble Factors,
which had been separately designated,
were in Fact either similar or identical sub-
stances. ±or example, the production oF EP
andLA±cou
ldbeshowntobest
imu
lated
b
yt
h
es
am
ea
g
en
t
san
dt
h
e
i
rm
o
l
e
c
u
-
lar weights (mw), isoelectric points (pI),
and other properties were broadly simi-
lar. Their purifcation initially showed that
they contained similar active, but heteroge-
nous, proteins with pIs ranging between
5 and 8. ±ollowing the coining oF ‘‘inter-
leukin’’ in 1979, LA± was redesignated as
interleukin-1. TCG± became interleukin-2.
This naturally started the quest For ‘‘discov-
ering’’ more interleukins and during the
1980s, with the major advance in rDNA
technology, many ‘‘new’’ interleukins were
cloned. Some oF these were clearly iden-
tical to specifc cell growth Factors, which
had been partially characterized earlier;
others turned out to be novel biologi-
cally active proteins. The new and ‘‘old’’
names For interleukins are summarized in
Table 1. New interleukins continue to be
identifed right up to the present day.
Once interleukins were cloned and made
available in large quantities via production
in recombinant bacteria, their biochem-
istry and biology could be and has been
thoroughly investigated. A common char-
acteristic that has emerged From such
studies is that most, iF not all, interleukins
have more than one biological activity and
there is Frequently an overlap between the
spectrum oF activities oF one particular
interleukin and another interleukin or a
member oF the cytokine superFamily, such
as an interFeron or a colony stimulating Fac-
tor. This indicates a signifcant redundancy
in the biological Functions oF interleukins
and oF cytokines in general. Such redun-
dancy suggests that interleukins trigger
convergent signaling pathways in cells,
and the more recent cloning oF inter-
leukin receptors has shed some light on
why this should be so. ±or instance, it is
now known that some interleukins share
nonspecifc receptor components besides
those components that are necessary For
specifc interleukin binding. ±urthermore,
while interleukin receptors do not contain
cytoplasmic kinase domains themselves,
it appears increasingly likely that they
are associated with a limited number oF
nonreceptor kinases, which mediate the
phosphorylation oF nuclear transcription
Factors. The latter are activated by this
process to bind to interleukin-responsive
elements oF interleukin-inducible genes
and activate their transcription. The subse-
quent expression oF interleukin-inducible
gene mRNAs and protein synthesis leads
to cellular responses. IF two (or more) inter-
leukins trigger the induction oF a common
set oF genes, then the observed cellular
response, For example, mitogenesis, will
probably be similar. However, cells have
regulatory mechanisms that control the ex-
pression oF interleukin receptors and thus
their responsiveness to particular inter-
leukins. Some interleukin receptors are
restricted to specifc cell types or lineages,
previous page 1439 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 1441 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off