Mediators of inflammation: classification

The appearance of inflammatory processes in response to the action of the pathological factor is an adequate reaction of the organism. Inflammation is a complex process that develops at the local or general level, arising in response to the action of foreign agents. The main task of the development of the inflammatory reaction is aimed at eliminating pathological influence and restoring the body. Mediators of inflammation are mediators who are directly involved in these processes.

Briefly on the principles of inflammatory reactions

The immune system is the guardian of human health. When necessary, it enters into battle and destroys bacteria, viruses, fungi. However, with enhanced activation of the work process of fighting against microorganisms can be seen visually or feel the appearance of a clinical picture. It is in such cases that inflammation develops as a protective response of the body.

There is an acute process of inflammatory reaction and its chronic course. The first occurs as a result of a sudden action of the irritating factor (trauma, damage, allergic effect, infection). Chronic inflammation has a protracted character and not so pronounced clinical signs.

In the case of a local response of the immune system, the following signs of an inflammatory reaction appear in the area of trauma or injury:

• Soreness;
• Swelling, swelling;
• Hyperemia of the skin ;
• Impaired functional state;
• Hyperthermia (rise in temperature).

Stages of development of inflammation

The process of inflammation is based on the simultaneous interaction of protective factors of the skin, blood and immune cells. Immediately after contact with a foreign agent, the body responds with local expansion of the vessels in the immediate trauma zone. There is an increase in the permeability of their walls and increased local microcirculation. Together with the blood flow, humoral protection cells come here.

In the second stage, immune cells begin to fight against microorganisms that are in the place of injury. A process called phagocytosis begins. The neutrophil cells change their form and absorb pathological agents. Further, special substances are allocated to destroy bacteria and viruses.

In parallel with microorganisms, neutrophils also destroy old dead cells located in the area of inflammation. Thus, the development of the third phase of the body's reaction begins. The focus of inflammation is, as it were, shielded from the whole organism. Sometimes pulsation can be felt in this place. Cellular mediators of inflammation start to be produced by mast cells, which allows to clean the injured area from toxins, slags and other substances.

General concepts of mediators

Inflammatory mediators are active substances of biological origin, which are accompanied by the main phases of alteration. They are responsible for the occurrence of manifestations of inflammatory reactions. For example, increased vascular wall permeability or local temperature increase in the area of trauma.

The main mediators of inflammation are allocated not only in the development of the pathological process. Their development occurs constantly. It is aimed at regulating the body's functions at the tissue and cellular levels. Depending on the direction of the action, the modulators have the effect:

• Additive (additional);
• Synergetic (potentiating);
• Antagonistic (weakening).

When a damage occurs or in the locus of microorganisms, the mediator link controls the processes of interaction of the inflammatory effectors and the change in the characteristic phases of the process.

Types of mediators of inflammation

All inflammatory modulators are divided into two large groups, depending on their origin:

1. Humoral: kinins, complement derivatives, factors of the blood coagulation system.
2. Cellular: vasoactive amines, arachidonic acid derivatives, cytokines, lymphokines, lysosomal factors, active metabolites of oxygen, neuropeptides.

Humoral mediators of inflammation are in the human body before the impact of the pathological factor, that is, the body has a stock of these substances. Their deposition occurs in cells in an inactive form.

Vasoactive amines, neuropeptides and lysosomal factors are also pre-existing modulators. The remaining substances that belong to the group of cellular mediators are produced directly in the process of development of the inflammatory reaction.

Complement derivatives

Mediators of inflammation include the derivatives of the compliment. This group of biologically active substances is considered the most important among humoral modulators. The derivatives include 22 different proteins, the formation of which occurs with the activation of complement (the formation of the immune complex or immunoglobulins).

1. Modulators C5a and C3a are responsible for the acute phase of inflammation and are liberators of histamine produced by mast cells. Their action is aimed at enhancing the level of permeability of vascular cells, which is carried out directly or indirectly through histamine.
2. The C5a des Arg modulator increases the permeability of venules at the site of the inflammatory reaction and attracts neutrophilic cells.
3. C3B promotes phagocytosis.
4. The complex C5b-C9 is responsible for the lysis of microorganisms and pathological cells.

This group of mediators is produced from plasma and tissue fluid. Through entering the pathological zone, there are processes of exudation. With the help of complement derivatives, interleukin, neurotransmitters, leukotrienes, prostaglandins and platelet activating factors are released.

Kininy

This group of substances is a vasodilator. They are formed in the tissue fluid and plasma from specific globulins. The main representatives of the group are bradykinin and callidin, the effect of which is manifested as follows:

• Participate in the contraction of the musculature of smooth groups;
• Due to the reduction of the vascular endothelium, the processes of wall permeability are enhanced;
• Contribute to an increase in arterial and venous pressure;
• Dilate small vessels;
• Cause the appearance of pain and itching;
• Contribute to the acceleration of regeneration and collagen synthesis.

The action of bradykinin is aimed at opening the access of blood plasma to the focus of inflammation. Kininy - mediators of pain of inflammation. They irritate the local receptors, causing discomfort, painful sensation, itching.

Prostaglandins

Cellular mediators of inflammation are prostaglandins. This group of substances refers to derivatives of arachidonic acid. The sources of prostaglandins are macrophages, platelets, granulocytes and monocytes.

Prostaglandins are inflammatory mediators that exhibit the following activity:

• Irritation of pain receptors;
• Vasodilation;
• Increased exudative processes;
• Increased hyperthermia in the lesion;
• Acceleration of the movement of leukocytes into the pathological zone;
• Increased swelling.

Leukotrienes

Biologically active substances related to newly formed mediators. That is, in an organism in a state of rest of the immune system, their quantity is not sufficient for an immediate response to the irritating factor.

Leukotrienes provoke an increase in the permeability of the vascular wall and give access to leukocytes in the pathology zone. They are important in the genesis of inflammatory pain. Substances are able to be synthesized in all blood cells, except for erythrocytes, as well as in the adventitia of lung cells, vessels and mast cells.

In case of development of the inflammatory process in response to bacteria, viruses or allergic factors of leukotrienes cause spasm of the bronchi, provoking the development of puffiness. The effect is similar to that of histamine, however, it is more prolonged. The target organ for active substances is the heart. Standing out in large numbers, they act on the cardiac muscle, slow the coronary blood flow and increase the level of inflammatory reaction.

Thromboxanes

This group of active modulators is formed in the tissues of the spleen, brain cells, lungs and blood cells of platelets. They have a spastic effect on the vessels, enhance the processes of thrombus formation in cardiac ischemia, promote the processes of aggregation and adhesion of platelets.

Biogenic amines

The primary mediators of inflammation are histamine and serotonin. Substances are provocateurs of initial microcirculatory disturbances in the pathology zone. Serotonin is a neurotransmitter that is produced in mast cells, enterochromaffins and platelets.

The action of serotonin varies depending on its level in the body. Under normal conditions, when the amount of the mediator is physiological, it increases the spasm of the vessels and increases their tone. With the development of inflammatory reactions, the amount increases dramatically. Serotonin becomes a vasodilator, increasing the permeability of the vascular wall and dilating the vessels. And its effect is a hundred times more effective than the second neurotransmitter biogenic amines.

Histamine is a mediator of inflammation, which has a multifaceted effect on blood vessels and cells. Acting on one group of histamine-sensitive receptors, the substance expands arteries and inhibits the movement of leukocytes. When exposed to the other, it narrows the veins, causes an increase in intra-capillary pressure and, on the contrary, stimulates the movement of leukocytes.

Acting on neutrophil receptors, histamine limits their functionality to monocyte receptors - it stimulates the latter. Thus, the neurotransmitter can exert an inflammatory, anti-inflammatory effect simultaneously.

The vasodilator effect of histamine is enhanced by the complex with acetylcholine, bradykinin and serotonin.

Lysosomal enzymes

Mediators of immune inflammation are produced by monocytes and granulocytes at the site of the pathological process during stimulation, emigration, phagocytosis, damage and death of cells. Proteinases, which are the main component of lysosomal enzymes, have an antimicrobial defense effect, lysing foreign exterminated pathogens.

In addition, the active substances contribute to increased vascular wall permeability, modulate leukocyte infiltration. Depending on the amount of enzymes isolated, they can enhance or weaken the migration of leukocyte cells.

The inflammatory reaction develops and lasts for a long time due to the fact that lysosomal enzymes activate the complement system, release cytokines and limokins, activate clotting and fibrinolysis.

Cationic proteins

Mediators of inflammation include proteins contained in neutrophilic granules and having a high microbicide. These substances act directly on the foreign cell, violating its structural membrane. This causes the death of a pathological agent. Further, the process of destruction and cleavage of lysosomal proteinases occurs.

Cationic proteins promote release of the neurotransmitter histamine, increase vascular permeability, accelerate the adhesion and migration of leukocyte cells.

Cytokines

These are cellular inflammatory mediators produced by the following cells:

• Monocytes;
• Macrophages;
• Neutrophils;
• Lymphocytes;
• Endothelial cells.

Acting on neutrophils, cytokines increase the level of permeability of the vascular wall. They also stimulate leukocyte cells to kill, absorb and destroy alien microorganisms that have settled, enhance the process of phagocytosis.

After killing pathological agents, cytokines stimulate the recovery and proliferation of new cells. Substances interact with representatives from their group of mediators, prostaglandins, neuropeptides.

Active metabolites of oxygen

A group of free radicals that, due to the presence of unpaired electrons, are able to interact with other molecules, taking a direct part in the development of the inflammatory process. Oxygen metabolites that are part of the mediators include:

• Hydroxyl radical;
• Hydroperoxide radical;
• Superoxide anion radical.

The source of these active substances is the outer layer of arachidonic acid, a phagocytosis explosion upon their stimulation, and the oxidation of small molecules.

Oxygen metabolites increase the ability of phagocytosis cells to kill foreign agents, cause fat oxidation, damage to amino acids, nucleic acids, carbohydrates, which increases vascular permeability. As modulators, metabolites can increase inflammatory phenomena or have an anti-inflammatory effect. Of great importance are the development of chronic diseases.

Neuropeptides

This group includes calcitonin, neurokinin A and substance P. These are the most known modulators from neuropeptides. The effect of the substances is based on the following processes:

• Attraction of neutrophils to the inflammation focus;
• Increased vascular permeability;
• Help with the influence of other groups of neurotransmitters on sensitive receptors;
• Increased sensitivity of neutrophils to the venous endothelium;
• Participation in the formation of pain in the process of inflammatory reaction.

In addition to all the above, active mediators include acetylcholine, epinephrine and norepinephrine. Acetylcholine takes part in the process of formation of arterial hyperemia, dilates the vessels in the focus of pathology.

Norepinephrine and adrenaline act as modulators of inflammation, inhibiting the growth of the level of vascular permeability.

The development of an inflammatory reaction is not a violation on the part of the body. On the contrary, it is an indicator that the immune system is coping with the tasks set.