MEDIATORS OF INFLAMMATION: AN INTRODUCTION
Author: Sanketh DS, MDS
Inflammation is fundamentally a protective response of the body against any offending agent or tissue damage. It involves responses of the vascular tissues, leukocytes, mast cells and macrophages which help in getting rid of the cause of tissue insult or injury. So, how is an inflammatory response triggered? Microbes, necrotic cells or tissue injury could trigger the release of certain soluble factors, from inflammatory cells, endothelial cells or from plasma. These soluble factors, called mediators of inflammation, initiate and amplify the inflammatory response and determine the consequent clinical and pathologic manifestations.
MEDIATORS OF INFLAMMATION
Mediators of inflammation are either cell derived or derived from plasma proteins.
Cell derived mediators of inflammation
When derived from cells, they could either be pre-formed, meaning they could already exist in the cell or could be newly synthesized. Let’s understand this better. Cells like mast cells, for example, have intra-cellular granules packed with chemical mediators called histamine. Mast cells, when stimulated, degranulate and release these already preformed chemical mediators to the environment eliciting inflammation. On the other hand, there are certain chemical mediators like prostaglandins or leukotrienes that are not pre-formed. They don’t exist in granules. They are rather newly synthesized in the cell with the help of certain enzymes, when needed. Leukocytes, mast cells, macrophages, platelets and even the endothelial cells could synthesize mediators of inflammation.
Cell derived preformed mediators of inflammation are histamine and serotonin. These factors are packed in granules of mast cells and platelets. Most other factors are newly synthesized and consist of various chemical mediators ranging from eicosanoids like prostaglandins and leukotrienes, pro-inflammatory cytokines like IL-1 and TNF-α, chemokines, platelet activating factor and free radicals like reactive oxygen species (ROS).
Plasma derived mediators of inflammation
Those factors that are plasma derived are proteins that are inactive in the circulation. These proteins could be stimulated by various factors and be activated, which then could trigger a cascade of reactions.
Plasma derived mediators are usually complement proteins C3a, C4a and C5a, kinins and proteases activated during coagulation.
PROPERTIES OF MEDIATORS OF INFLAMMATION
Chemical mediators of inflammation are only stimulated by factors like microbes, foreign agents, damaged and necrotic tissue. Usually these are factors or molecules that can trigger inflammation through various receptors and other pathways. This way, there is a check to which molecules trigger inflammation.
A chemical mediator could stimulate the production or release of another mediator. A common example would be pro-inflammatory cytokine TNFα acting on the endothelium, which in turn produces cytokine, IL-1. Also, complement proteins like C3a and C5a could stimulate mast cells to degranulate and release histamine.
Different chemical mediators could share the same function and any one chemical mediator could have more than one function.
Different mediators, same function:
Mediators like histamine, serotonin and leukotrienes could cause an increased vascular permeability of the blood vessels. Also, complement proteins like C3a and C5a and leukotriene B4 are chemotactic factors, that help recruit neutrophils to the site of inflammation.
One mediator, different functions:
Complement proteins like C3a and C5a, besides being anaphylatoxins stimulating mast cell degranulation, are also chemotactic factors helping attract neutrophils to the site of inflammation.
Most chemical mediators are short lived. Once their function is done, they either quickly decay or are inhibited/stopped from functioning, so there is a check or balance maintained with regards to the inflammatory reactions instigated.
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