Inflammation. Inflammation mediators
There are two types of inflammatory mediators. Cell derived mediators, and plasma derived mediators. We have tabulated the core ones below.
Cell derived mediators
Plasma derived mediators
Remember: the main mediators of each effect:
- Vasodilation: histamine, prostaglandins, nitric oxide
- Increased permeability: histamine, bradykinin, C3a and C5a, leukotrienes C4, D4, E4
- Chemotaxis: C5a, leukotriene B4, IL-8 (CXCL8), bacterial products
- Fever: IL-1, TNF, prostaglandin E2
- Pain: bradykinin, prostaglandin E2
So, let's take a quick look at some of those systems that we’ve just mentioned.
Kinin system
- Mediated by bradykinin and kallidin, two vasodilators
- Plays a role in inflammation, blood pressure, coagulation and pain control
- In effect, activated factor XII (Hageman factor) forms Kallikrein, this in turn converts Kininogens into Kinins.
- Kinins (such as bradykinin) then go on to act to:
- Stimulate complement system
- Promote vasodilation and increase capillary permeability
- Activate pain receptors
- Act as chemotaxins
Complement system
This is the name we give to the biochemical cascade of the immune system that allows the body to activate an immune response and organise its tools.
It consists of around 30 complement proteins in the blood, synthesized by the liver, they augment the function of the immune system by opsonization, membrane attack complex formation and enhancing inflammation.
Opsonization
- The coating of a pathogen with complement proteins to make phagocytosis by macrophages easier thanks to receptor binding
Membrane attack complex
- Create a membrane attack complex where a group of proteins make holes in the membrane of the pathogen
The proteins travel around the body in an inactive form, and only become activated when they come into contact with a pathogen or are activated by other complement proteins. The way in which a complement protein becomes active can be via a Classical, Alternative or Lectin pathway.
All of these pathways help to split (cleave) the Complement 3 (C3) protein into C3a and C3b. C3a assists within inflammation while C3b assists in Opsonization and the formation of membrane attack complexes.
Classical pathway
- Initiated when Antibodies bind to Antigens. A C1 complex then binds to the antibodies, forming the C4b2a complex.
- C4b2a complex then sits on surface of pathogen and splits C3 into C3a and C3b (it is the classical C3 convertase)
Alternative pathway
- Activated directly on microbial surfaces by spontaneous C3 hydrolysis; it also amplifies the C3b made by the Classical (or lectin) pathway.