00:01
How do we resolve the
acute inflammatory process?
Well, we have to inactivate
all the mediators.
00:07
Fortunately, many of these
are very short lived,
although they're very potent,
and can cause a lot of damage
most spontaneously will decay.
00:16
So the eicosanoids
that we talked about
those molecules that
come from arachidonic acid,
tend to fall apart
relatively quickly.
00:23
Nitric oxide also tends
to fall apart relatively quickly.
00:27
So there's spontaneous decay.
00:30
We are releasing into the space,
a lot of proteases.
00:34
And those will catabolize
or break down enzymes
and other proteins.
00:39
So we will have kind of
a major debris field
as we chew up
everything in that area.
00:45
And that will also inactivate
many of the mediators.
00:49
We have a number of scavengers
for oxygen free radicals.
00:52
Remember, oxygen free radicals?
Reactive Oxygen Species,
or ROS
are going to be really important
in terms of cleaning up and
sterilizing the area of injury.
01:04
We have to scavenge those,
and we have a number of molecules
that will do that.
01:10
We have inhibitors.
01:11
This is one of those paradigms
that we've talked about.
01:13
Every time you have something
that's pro inflammatory,
such as complement,
you have actually
anti inflammatory pathways
that will inhibit.
01:20
So we are also elaborating those
in this timeframe.
01:25
And we will make
counter regulatory molecules.
01:28
So remember,
even as we're making
pro inflammatory prostaglandins
and leukotrienes from those
arachidonic acid metabolites,
on the other hand, we're also
making anti-inflammatory lipoxins.
01:41
So this is going to be
how we inactivate
many of the mediators,
or fine tune them
to turn down all of the inflammation
coming from the neutrophils.
01:53
The other thing is that
we're going to stop
recruiting those neutrophils.
01:56
We are going to change
the endothelium.
01:58
It's not going to be sticky anymore,
specifically for neutrophils.
02:03
And the neutrophils
that have crawled across,
they're very short lived.
02:06
Within 10 hours,
they undergoes cellular suicide.
02:11
It's actually kind of interesting.
There are some disease states
where the neutrophils live
two to three hours longer
than they're supposed to.
02:18
And those patients,
every time they get
a little bit of an infection
or a little bit of an injury,
have a very aggressive
inflammatory response
and actually get more
tissue necrosis.
02:28
So we count on the neutrophils
killing themselves
after about 10 hours
after they crawl out
of the blood vessels.
02:35
Were also one of the
other mechanisms
for modulating
acute inflammation
is to modulate
the receptor expression
or signal transduction of
many of the cells in the area.
02:46
So mast cells, fibroblasts,
smooth muscle cells,
everything that's in the area.
02:52
As they have been
stimulated once
they tend to internally
counter regulate
and turn down the receptors
so they're not as susceptible
to signaling
as they were previously.
03:02
So there are many ways
that we can moderate
resolve the acute inflammation.