What Are Mediators Of Inflammation, Part 2
In part 1, I defined mediators of inflammation. In this post, I am going to list the mediators that are responsible for asthma. It's good to know these because some of our newer medicines and biologics target these. Furthermore, others listed here are being targeted by treatments currently in the pipeline. So, here's some of your mediators of inflammation.
Mediators released from mast cells include the following
Histamine. They are released by mast cells and other cells too during allergy and asthma attacks. 2,4 They were first discovered in 1910 by Henry Hallett Dale,3,5 are mainly responsible for upper airway inflammation resulting in allergy symptoms such as itchy, stuffy, runny nose, sneezing, etc. They also cause inflammation of the conjunctiva of the eyes, causing dry, itchy, watery eyes, etc.
Leukotrienes. First discovered in 1938 to cause bronchospasm, they are now thought to mediate cause airway inflammation and directly cause bronchospasm, and are responsible for both allergy and asthma symptoms. While histamine does the same thing, leukotrienes are 3-4 times more potent and stick around longer. Some may also leave the airways to recruit eosinophils (involved in the late phase asthma attack I will delve into in my next post).4,6
Prostaglandins. They are released by mast cells in allergic asthma. They mediate airway inflammation. Common ones are Prostaglandin D2 (PgD2), which causes airway inflammation, increased mucus production, and bronchoconstriction.2,5-8
Chemokines. They are a special kind of cytokine whose production is triggered by cytokines (many are released from airway epithelial cells, or cells lining airways, along with tissue fibroblasts, of which we will not define at this point).8 They circulate through your bloodstream to recruit more leukocytes to the scene. The leukocytes recruited are responsible for the late phase asthma attack (again, I will discuss this late phase in my next post)
Here is a sample of some chemokines that play a role in asthma.
CCL11/eotaxin: It’s a chemokine made by the CCL11 gene. It recruits even more eosinophils. So, as you can see, many eosinophils are on the way. They play a key role in the Late Phase asthma/ allergic response. They will start arriving in about four hours.2,5,7,8,10
CCL17/TARC: It’s a chemokine made by the CCL17 gene. It’s secreted by dendritic cells and plays a role in the development of T-Cells in the thymus, and then the activation and maturation of them. For our purposes, they recruit more Th2 cells to the scene.9,11 (You should start getting the idea of why this entire immune response is often referred to as the Th2 Dominant Response. I will describe this asthma subgroup in an upcoming post.)
CCL22/macrophage-derived chemokine MDC: It’s a chemokine made by the CCL22 gene. It’s secreted by dendritic cells and macrophages, and attracts monocytes, dendritic cells, and natural killer cells to the scene.7,8,10,12
See, so all of these other immune cells are being recruited to the scene. They are on the way. This is good if you have a pathogen like a respiratory virus infecting your airways. But, in our case, this is bad. It means you’ll probably experience more severe asthma during the Late Phase Asthma Attack.
So, now you know what mediators of inflammation are. You also know what some of the most common mediators are. In my next post, I’m going to describe what happens during the last phase asthma attack. And if I mention mediators, at least now you have a better idea of what I’m talking about.
Have you ever gotten "moon face" as a side effect of prednisone?