So that’s acute inflammation.
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.
Chronic inflammation can also arise insidiously,
without any kind of obvious reason.
There is a T-cell and
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.
As well as tumor necrosis
factor alpha, and interferon γ.
And these pro-inflammatory cytokines
recruit and activate macrophages.
And re-macrophage activation
is key in chronic inflammation.
In chronic inflammation, the macrophages become
activated by microbial products and cytokines.
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.
These macrophages have the characteristics
of being pro-inflammatory, they
perpetuate the inflammatory process
and they are also highly phagocytic.
And they perpetuate the inflammatory process
by they themselves releasing pro-inflammatory cytokines,
such as tumor necrosis factor
alpha, interleukin-12 and interleukin-23.
And a consequence of the release
of these cytokines by macrophages
is that they increase the activity of Th1 cells and Th17 cells.
These are two types of helper T-cells.
Both of which are involved
in chronic inflammation.
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.
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).
So these are not directly
involved in chronic inflammation.
They are anti-inflammatory, in contrast to the
M1 macrophages that mediate chronic inflammation.
And whether the macrophage develops
into an M1 or an M2 macrophage
depends on which cytokines and which
microbial products are present.
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.
Chronic inflammation contributes towards
pathology in many, many, many different diseases.
And in fact, there’s probably very few diseases where
chronic inflammation doesn’t play some role or another.
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.