Inflammation- Process, Factors, and Anti-Inflammatory agents
Introduction
Inflammation is an intricate response to various stimuli which includes local trauma, wound, or infections.
Several mediators such as chemokines, cytokines, and immune cells such as neutrophils, macrophages are involved in process of inflammation.
Its characteristics can be determined by heat, redness, swelling, and pain at the site of injury or trauma.
Overview of the Inflammation process
Steps involved in the process of Inflammation
The inflammation process is activated when there is tissue damage caused by injury or trauma, it includes series of collective events to execute the inflammatory response.
It is triggered by the component of the pathogen for e.g., LPS( Lipopolysaccharide) present in the bacterial cell wall, interacts with the cell surface receptors.
The steps involved in this process are as follows:
Injury leading to tissue damage causes secretion of chemotactic and vasoactive factors, triggering vasodilation, and an increase in capillary permeability.
Exudates and cells are marginalized to the endothelial wall of the blood vessel, and cells migrate to the inflammation sites through the permeable capillaries by the process of extravasation or diapedesis (cells oozes out through permeable capillaries).
Eventually, phagocytic cells ( by the process of phagocytosis) and antibacterial exudates kill the bacteria.
A detailed explanation of the inflammation process
There are two types of inflammatory response that have been introduced are as follows:
Acute Inflammatory Response
Chronic Inflammatory Response
Generally, acute inflammation is rapidly active and is short-term, it is followed by a systemic( includes whole body system)Â reaction which is termed as the acute phase response, in which various plasma proteins alterations is involved.
Chronic inflammation is induced when the antigen is persistent( pathogen escapes the phagocytosis)Â and causes pathological aftereffects. Also involved in allergy and autoimmune disorders.
Factors involved in the Inflammatory Response
Neutrophils play a major role in the early inflammation process
During, early inflammatory response, neutrophils infiltrate the tissue predominantly, production of neutrophils peaks within 6 hr of response.
Generally, more than 1000 neutrophile is produced per day but it may increase tenfold during the process of the acute inflammation.
When acute inflammation is mediated, neutrophils are attached or tethered to the endothelial walls of blood vessels with the help of the expression of E- selectin(enhanced by IL-1 or TNF), and P- selectin(enhanced by Histamine and Thrombin).
Neutrophil adhesion and following migration through a transendothelial wall is mediated by the chemokines for e.g., IL-8 or other chemoattractants activates the G- signaling pathway which alters the conformation of integrin adhesion molecules.
The activated neutrophils exhibit chemotaxis by expressing the elevated levels of chemoattractant receptors. Some other chemotactic mediators for neutrophils are as follows:
Several inflammatory mediators such as chemokines, complement products (C3a, C5a), leukotriene, prostaglandins.
Even molecules such as formyl methionyl peptides are released by microorganisms.
Expression of Fc receptors of complement & antibody in increased levels on activated neutrophils enhanced the binding of the phagocytosis.
The activated signals trigger the pathway of respiratory burst, generate reactive oxygen and nitrogen intermediates, release this substance cause tissue damage.
The collective accumulation of dead microorganisms &Â cells including fluids and proteins is termed pus.
Inflammation Response can be Localised or Systemic
As tissue injury, mediate the non-specific complex events that are called the inflammatory response, helps to restrict the damage of the tissues to the initial site of the trauma or infection. Acute inflammation involves both systemic & localized responses.
Localized Inflammatory response
The indication of such responses is redness (RUBOR), heat (CALOR), pain (DOLOR), swelling( TUMOUR), and function loss at the site of the injury or infection.
In a minute after tissue damage, vasodilation occurs i.e., the diameter of capillaries increases; which leads to a rise in the volume of blood at the affected region( cause heat and reddening of the tissue)Â & also blood flow is reduced.
The above event leads to leakage of the exudates from the vessels of the blood, which causes fluid accumulation (edema) in the tissues and also diapedesis i.e., oozing out of the leukocytes results in swelling and redness in the affected area.
Exudates leakage in the tissues activates kinin, fibrinolytic component, and clotting system.
Vascular changes such as an increase in vascular permeability and vasodilation are mediated by plasma enzymes for e.g., fibrinopeptides, bradykinins, prostaglandins, and complement anaphylatoxins(C3a, C4a, and C5a), which promotes degranulation of the mast cell, which releases Histamine, an effective mediator of inflammation.
Adherence of neutrophils to the endothelial cells, and migration to the affected site take place, which leads to phagocytosis, which releases mediators such as MIP-α and β  (chemokines) which attract macrophages.
 Macrophages enhance the clearance of pathogens by the increased the phagocytic process. It releases cytokines such as IL-1, IL-6, and TNF which involve in the inflammatory response.
The cytokines facilitate both marginalization and migration of the immune cells to the endothelial cells and also enhance the influx of the immune cells which helps in the clearance of pathogen and tissue healing.
The tissue healing is induced by TGF-β, by restricting the inflammatory response and facilitating fibroblast accumulation & proliferation.
Systemic Acute Phase inflammatory response
Usually, the localized inflammatory response is followed by the systemic response termed as an acute-phase response.
Hallmarks are fever, elevated synthesis of hormones for e.g., hydrocortisone and ACTH, WBC, and in the liver, there are high numbers of acute-phase proteins.
The rise in body temperature restricts the number of pathogenic growth and enhanced immune responses.
Acute-phase response elevates serum level up to 1000 fold of C- reactive proteins, activates complement which leads to deposition of the C3b opsonin on the pathogen cell surface, as phagocytic cells express receptors for c3b, the pathogen is readily phagocytosed.
The effects of acute-phase response are combinedly carried out by cytokines, are IL-1, TNF β, and IL-6, they induce fever by acting on the hypothalamus.
When antigen persists in the body system, the Chronic Inflammatory Response is developed
Few pathogens have a tendency to evade phagocytosis, which induces a chronic inflammatory response that causes tissue damage.
In autoimmune disease, cancer, and tissue damage, the chronic inflammatory response is observed.
The significant hallmarks are macrophage activation and its accumulation.
In the formation of scar tissues, fibrosis, a wound healing process is involved at the affected area which affects the tissue normal function, and also granuloma formation(tumor-like growth ), is observed.
In the development of chronic inflammation, two cytokines such as IFN-γ (released by TH1, TC, and NK cells )and TNF-α (released by macrophages) play a significant role.
Anti-inflammatory agents
Although inflammation plays a significant role in the defense system, sometimes it’s harmful; during allergies, burns, transplants, autoimmune disease, it may induce chronic inflammation process, to reduce such long-term response, therapeutic measures have been introduced.
To reduce the leukocyte extravasation in the inflammation process, antibody therapy is used. For e.g., Antibodies ICAM-1 protect the tissues from necrosis in burn patients.
Anti-inflammatory drugs such as Corticosteroids, cholesterol derivatives include prednisone, prednisolone & methylprednisone, which decreases the numbers and immune system activity such as leukocyte migration, phagocytosis, chemotaxis, etc.
NSAIDs (Nonsteroidal anti-inflammatory drugs), e.g., ibuprofen, Aspirin, Naproxen used as pain relievers and to treat inflammation.
