Cytokines: Interleukins
127
Tab. 3
Interleukins and cytokines secreted by T-helper CD4
+
cell subsets and cytotoxic CD8
+
T
lymphocytes.
Interleukin/cytokine
Th1
Th2
Th0
Cytotoxic T
lymphocytes (CTL)
Interferon-
γ
(IFN
γ)
+
+−+
+
+
+
IL-2
+
+−+
+
±
IL-3
++
++
++
+
IL-4
−+
+
+
+
IL-5
−+
+
+
+
IL-6
−+
++
IL-9
?
?
+
?
IL-10
−+
+
+
+
?
IL-13
−+
+
??
GM-CSF
++
+
+
++
Tumor necrosis factor-
α
(TNF
α
)
++
+
?
+
Tumor necrosis factor-ß (TNFß)
++
?
+
nor mature forms appear to enter the en-
doplasmic reticulum as would a ‘‘normal’’
secreted protein). Some IL-1
α
appears to
remain ‘‘anchored’’ in the cell membrane
or the cell associated for several hours
before being released, whereas IL-1ß is
quickly ‘‘secreted’’. The processing of IL-
1
α
and ß is unusual and for all of the other
interleukins, including IL-1ra, processing,
posttranslational modiFcation, for exam-
ple, glycosylation, and secretion occurs
through the regular route for a protein
containing an N-terminal signal sequence,
that is, via the endoplasmic reticulum and
the Golgi apparatus.
The expression of all the interleukin
genes is tightly regulated. Interleukin mR-
NAs
are
usually
made
for
only
short
periods of time following induction. The
interleukin genes then become hypore-
sponsive to further stimulation, probably
due to increases in the level of repres-
sor complexes. Synthesis of interleukins
is also of a relatively short duration, but
can depend on the stability of the mRNA.
In addition, the level of synthesis will
be affected (modulated) by the presence
of
other
active
regulatory
agents
[(for
example, immunosuppressive hormones
(prostaglandins, glucocorticoids) and cy-
tokines (transforming growth factor beta
TG±-
β
)].
The major cell sources and inducers
of particular interleukins are detailed in
Table 4.
3
Interleukin Receptors
3.1
Receptor Structure
As discussed in Sect. 2.1, many
inter-
leukins
have
similar
α
-helical
bundle
structures and therefore it is not sur-
prising that their cell surface receptors
also share common structural features,
particularly in their N-terminal extracel-
lular binding domains. The receptors for
IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-12, IL-
13, IL-15, and IL-21 have been classiFed
under the generic name of hematopoi-
etin receptor (HR). Alternatively, they are
known as type I cytokine receptors. Two
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