We’ve heard quite a
lot about cytokines.
Let’s explore them in a
little bit more detail.
What exactly are they?
And what exactly do they do?
And how do they do it?
Well, they tend to be rather small molecules,
typically kind of in the range of 8-80 kilo Daltons.
They’re secreted proteins, and really
they act as messengers between cells.
We can group them into sort of, five or
so major groups: the interleukins, the
colony-stimulating factors, chemokines, the
interferons and the tumor necrosis factors.
Some people classify chemokines independently of cytokines,
but essentially they are chemotactic cytokines.
They are great at multitasking.
I don’t think there’s any example of a
cytokine that just does one single job.
They tend to have multiple roles.
And they have multiple functions collectively, that
include control of hematopoiesis and immune responses.
And they function by binding
to specific cytokine receptors.
So for example, the cytokine interleukin-1,
there’ll be an interleukin-1 receptor;
the cytokine interleukin-2, there’ll be
an interleukin-2 receptor and so forth.
And when the cytokine binds to its receptor, it results
in initiating an intracellular signaling cascade.
And this signaling can lead either to the
up-regulation or down-regulation of genes.
And those genes can encode other cytokines, may encode cell
surface molecules, other secreted molecules of various types.
They may be genes that control cell proliferation
or control cell differentiation, or cell survival.
So let’s just go through the different groups of
cytokines and pick out a few important points.
Interferons, as their name suggests,
interfere with viral replication.
And there are two main types of
interferon - type I and type II.
Type I are interferon-alpha
And these two particular interferons are
produced by most nucleated cells of the body.
In contrast, Type II interferon which is gamma interferon,
is produced by a rather limited group of cells
- natural killer cells, Th1 cells and Tc1 cells, are
particularly good at producing gamma interferon.
It promotes the production of Th1 cells,
but inhibits the production of Th2 cells.
It’s important in
And it can increase the expression of both MHC
Class I and MHC Class II on the surface of cells.
The interleukins, as their name
suggests, acts between leukocytes.
So that’s where the term comes; inter-
between, leukocytes, interleukins.
And there are around about
40 different interleukins.
New ones are being discovered every once in
awhile, and whether a particular cytokine is given
the designation interleukin or given some other
designation, is to be honest rather arbitrary.
Interleukin-1 is produced by macrophages
and dendritic cells, and it’s a
pro-inflammatory cytokine; groups of
cytokines that tend to promote inflammation.
And interleukin-1 is
one of those cytokines.
Interleukin-2 is characteristically produced by Th1
cells, and it promotes both T and B-cell proliferation.
IL-4 is produced by Th2 cells, and it
promotes Th2 cell differentiation and is
particularly important in class switching
B-cells to produce the IgE class of antibody.
IL-10 very characteristically produced by regulatory T-cells,
it down-regulates responses and therefore is anti-inflammatory.
IL-12 just like IL-1 is produced predominantly by macrophages
and dendritic cells, and it promotes Th1 cell differentiation.
IL-13, product of Th2 cells,
promotes B-cell proliferation.
IL-17, produced by Th17 cells is
pro-inflammatory and Th17 cells
also produce interleukin-22, which is again pro-inflammatory.
So these are just some,
picked out of those 40 or so.
Some of the more commonly discussed
cytokines that are interleukins.
What about the
Well these are secreted by a variety
of cell types, including bone marrow
stromal cells, that is cells
like fibroblasts and macrophages.
And there are three main types:
factor (GM-CSF), which acts early in myeloid development.
Monocyte macrophage colony-stimulating factor
(M-CSF), which induces monocyte differentiation.
And granulocyte colony-stimulating factor (G-CSF), which
induces granulocyte differentiation as its name suggests.