Chronic Inflammation

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.