Inflammation is fundamentally, a protective response of the body against any offending agent or tissue damage. It involves responses of the vascular tissues and leukocytes which help in getting rid of the primary cause of insult and necrotic cells or tissues resulting as a consequence of the insult. Inflammation could be acute or chronic depending on the duration of the response.
Acute inflammation is a rapid response, developing within minutes and could last up to a few hours to days. If the insult or damage is not repaired by the acute response, the inflammatory response could become prolonged thus becoming Chronic. Chronic inflammation could go on for few weeks to many months.
Inflammation could be caused by multiple factors ranging from external agents like microbes, drugs and allergens, physical agents like temperature, any form of mechanical injury and other factors like genetic and immunologic disorders. Tissue necrosis due to ischemia, mechanical or chemical injury could also induce inflammation.
Cardinal signs of Inflamatin
There are 5 cardinal signs of inflammation, which actually are a macro-level or an external manifestation of the microscopic events happening during inflammation.
- Inflammation kick starts with vasodilation of arterioles and capillaries near the site of tissue insult and this leads to “RUBOR”or redness.
- Vasodilation results in increased blood flow causing “CALOR” or heat.
- Leakage of plasma fluids from the vessels and accumulation in the extra-vascular space causes “TUMOR” or swelling.
- Chemical mediators of inflammation like histamine and prostaglandins may cause “DOLOR” or pain.
- Swelling and pain may cause loss of function, of the tissue involved and is called “FUNCTIOLAESA” or loss of function.
An inflammatory response begins with an insult which could be exogenous or endogenous. Any form of insult causes cell damage and damaged cells release certain molecules are called “Damage Associated Molecular Patterns (DAMPs)”.
These molecules are recognised by receptors on leukocytes like macrophages or dendritic cells. On recognition leukocytes release pro-inflammatory cytokines.
Similarly microbes have specific molecules called “Pathogen Associated Molecular Patterns (PAMPs)” which could be recognised by receptors on leukocytes. On recognition leukocytes release pro-inflammatory cytokines and also other cytokines that help lymphocyte activation.
Now, pro-inflammatory cytokines could cause degranulation of nearby mast cells. Degranulation results in release of inflammatory mediators like histamine, eicosanoids like prostaglandins, leukotrienes and more pro-inflammatory cytokines.
This cascade of events kick starts an acute inflammatory response. Acute inflammation begins with vasodilation of arterioles and capillaries. Vasodilation could be caused by histamine, leukotrienes and prostaglandins.
This is followed by an increased vascular permeability. So Histamine and leukotrienes can cause retraction of the endothelial cells in the vessels creating small gaps. and Plasma proteins leak out of the blood vessel through these gaps and accumulate in the extra-vascular space causing oedema.
This plasma rich fluid leaking out of the vessel and accumulating in the extravascular space is called an exudate.
Leakage of plasma proteins disturbs the axial flow of blood. It increases blood viscosity thereby slowing down or causing stasis of blood flow. This results in red blood cells getting concentrated at the centre with leukocytes being pushed to the periphery near the vessel wall.
Acute inflammation serves to recruit leukocytes to the site of infection or injury in order to eliminate the offending agents and damaged tissue. Neutrophils and monocytes are key leukocytes that are recruited and are capable of phagocytosis.
However in acute inflammation, neutrophils are the first batch of leukocytes to be recruited to the site of infection. Migration of monocytes follows many hours later. Leukocyte recruitment to the site of infection involves a series of steps.
Once the blood flow slows down, leukocytes are pushed to the periphery and move along in close association to the endothelium. This process is called margination.
Pro-inflammatory cytokines like IL-1 and TNF-α released by macrophages and mast cells cause endothelial cells and leukocytes to express what are called adhesion molecules.
Adhesion molecules on the endothelium are called selections and those on leukocytes are called sialyl Lewis X proteins. Sialyl Lewis X proteins bind with selections causing leukocytes to slow down and tumble along the endothelium, a process called 'rolling'. Rolling and slowing down, helps leukocytes firmly adhere to the endothelium. This is accomplished by binding of surface proteins on leukocytes called integrins to adhesion molecules on the endothelium called, VCAM – vascular cell adhesion molecule.
Expression of VCAMs on the endothelium are induced by pro-inflammatory cytokines like IL-1 and TNF-α.
The next step involves the transmigration of adherent leukocytes through the endothelial gaps to the extravascular space. This process called diapedesis is induced by chemokines. Once in the extravascular space, leukocytes migrate towards the site of infection along a concentration gradient, a process called chemotaxis.
Chemotaxis is induced by a variety of chemokines produced by mast cells, complement proteins and the microbes themselves. Examples of chemokines are IL-8, LTB4 and complement proteins like C5a.
Neutrophils predominate in the site of infection for the first 6-24 hours followed by monocytes getting into action post 24-48 hours. After recruitment to the site of infection leukocytes recognise microbes or dead cells and kill them by a process called phagocytosis.
