Resolution of Acute Inflammation

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.