134
Cytokines: Interleukins
mimic the
in vivo
situation and experimen-
tally a highly reductionist approach using
isolated molecules, isolated cells, and cell
lines has formed the basis for studying
the biological activities of individual in-
terleukins. Such work has provided an
important base, but is unsatisfactory in the
long run as the true roles of interleukins
cannot be accurately predicted. Only stud-
ies in whole animals and intact tissues
will provide answers on the physiological
importance of interleukins.
This section will Frst concisely review
the biological activities of interleukins,
starting with IL-1, that have been deFned
from
in vitro
experimentation. However,
thevas
tamoun
to
fl
i
tera
turein
forma
t
ion
precludes a totally comprehensive survey.
Secondly, some examples of interleukin
interactions will be briefly described and
thirdly, the
in vivo
biological roles of in-
terleukins, where information is available,
will be outlined.
4.1
Interleukin-1
An unusually large number of biologi-
cal activities have been attributed to IL-1.
Broadly speaking, the activities of IL-1
α
and IL-1ß are qualitatively the same, and
both IL-1
α
and ß are antagonized by IL-1ra.
Currently, the activities of other members
of the IL-1 superfamily, excluding IL-18,
are not known. In general, IL-1
α
and ß
behave as the primary activators of cells,
readying them for secondary stimuli. As
such, they have been included in a cate-
gory of mediators called
competence factors
.
These are considered to be elements of cell
activation pathways, which commit cells to
a series of stimulatable, contingent events.
In this context, IL-1 has been shown to
augment antigen activation of T lympho-
cytes and to potentiate the proliferation of
hematopoietic progenitors. IL-1 has also
been demonstrated to induce the synthesis
of secondary acting mediators, the so-
called
progression factors
that stimulate cells
to undergo further proliferative or differen-
tiating events. ±or example, IL-1 induces
platelet-derived growth factor (PDG±), a
potent
mitogenic factor,
in Fbroblasts,
GM-CS± in endothelial cells, IL-2 in T lym-
phocytes and IL-1, IL-6, IL-8, and TN±
α
in
monocytes/macrophages. In addition, IL-
1 can induce or regulate the expression of
receptors and other cell surface molecules,
for example, IL-2R
α
in T lymphocytes,
ICAM-1, and VCAM-1 in endothelial cells.
IL-1, at least
in vitro
, can stimulate acute-
phase protein synthesis in hepatocytes,
although it is not as potent as IL-6 (NB
possibly the effects of IL-1 on hepatocytes
occur as the result of intermediate produc-
tion of IL-6). At relatively high doses, IL-1
induces bone and cartilage resorption
in
vitro
cell systems. In contrast, at low doses,
IL-1 may promote osteoblast proliferation
and transiently stimulate collagen syn-
thesis. IL-1 induces prostaglandin (PGE
2
)
synthesis by synovial cells.
In hematopoiesis, that is, the generation
of mature blood cells from bone marrow
stem cells, IL-1 can act as activator of
early
progenitors,
and
in
combination
with other interleukins, for example, IL-3,
IL-6, it probably stimulates proliferation
and
differentiation
of
the
various
cell
lineages. It may synergize with IL-6 for
IL-2 synthesis by activated T lymphocytes,
with
IL-4
for
B-cell
activation
and
Ig
isotype
regulation,
and
with
IL-2
or
I±N for augmenting natural killer (NK)
cell activity.
In vivo
, IL-1 is known to induce fever
(IL-1
was
originally
called
endogenous
pyrogen
(
EP
)), sleepiness, and anorexia.
IL-1 also has been shown to affect the
neuroendocrine
system,
principally
by
previous page 1454 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 1456 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off