00:01
So that’s acute inflammation.
00:03
What about chronic inflammation?
Well, chronic inflammation occurs when there
is a failure to eliminate the stimulus
which results in an ongoing inflammatory immune response
with a shift away from neutrophil dominance.
00:20
Chronic inflammation can also arise insidiously,
without any kind of obvious reason.
00:29
There is a T-cell and
macrophage dominance.
00:33
T-cells and NK cells release pro-inflammatory
cytokines such as interleukin-17--
so here’s another example of a pro-inflammatory
cytokine that you’ve not met yet.
00:45
As well as tumor necrosis
factor alpha, and interferon γ.
00:51
And these pro-inflammatory cytokines
recruit and activate macrophages.
00:56
And re-macrophage activation
is key in chronic inflammation.
01:02
In chronic inflammation, the macrophages become
activated by microbial products and cytokines.
01:11
So we can see in this particular
example, lipopolysaccharide (LPS) from
Gram-negative bacteria together with the
cytokines, tumor necrosis factor alpha and
interferon gamma are classically
activating the macrophage to produce what is
referred to as an M1 macrophage, a
classically activated M1 macrophage.
01:32
These macrophages have the characteristics
of being pro-inflammatory, they
perpetuate the inflammatory process
and they are also highly phagocytic.
01:43
And they perpetuate the inflammatory process
by they themselves releasing pro-inflammatory cytokines,
such as tumor necrosis factor
alpha, interleukin-12 and interleukin-23.
01:55
And a consequence of the release
of these cytokines by macrophages
is that they increase the activity of Th1 cells and Th17 cells.
02:08
These are two types of helper T-cells.
02:10
Both of which are involved
in chronic inflammation.
02:16
Alternatively, in the presence of cytokines such as
interleukin-4, interleukin-13, interleukin-10
and transforming growth factor β (TGFβ), you get M2 macrophages
being produced; alternatively activated macrophages.
02:35
And these are anti-inflammatory and are
involved in tissue repair, and secrete
cytokines such as interleukin-10 and the
interleukin-1 receptor antagonist (IL-1RA).
02:49
So these are not directly
involved in chronic inflammation.
02:53
They are anti-inflammatory, in contrast to the
M1 macrophages that mediate chronic inflammation.
03:01
And whether the macrophage develops
into an M1 or an M2 macrophage
depends on which cytokines and which
microbial products are present.
03:09
So chronic inflammation is associated
with tissue damage and the M1 macrophage
is important in this process because of
several features that are characteristic
of M1 macrophages: the production of
reactive oxygen species, the production of
nitric oxide, the production of proteases
and the release of coagulation factors.
03:33
Chronic inflammation contributes towards
pathology in many, many, many different diseases.
03:41
And in fact, there’s probably very few diseases where
chronic inflammation doesn’t play some role or another.
03:47
To give you just a few examples: rheumatoid arthritis,
atherosclerosis, tuberculosis, pulmonary fibrosis,
cancer, and Alzheimer disease; just a few examples of diseases
where chronic inflammation is key to the disease process.