The appearance of inflammatory processes in response to the action of a pathological factor is an adequate response of the body. 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 the pathological influence and restoring the body. Inflammatory mediators are mediators directly involved in these processes.
Briefly about the principles of inflammatory reactions
The immune system is the guardian of human he alth. When the need arises, it enters into battle and destroys bacteria, viruses, fungi. However, with increased activation of work, the process of combating microorganisms can be seen visually or the appearance of a clinical picture can be felt. It is in such cases that inflammation develops as a protective response of the body.
Distinguishacute process of inflammatory reaction and its chronic course. The first occurs as a result of the sudden action of an irritating factor (trauma, damage, allergic influence, infection). Chronic inflammation has a protracted nature and less pronounced clinical signs.
In the case of a local response of the immune system in the area of injury or injury, the following signs of an inflammatory reaction appear:
- soreness;
- swelling, puffiness;
- skin hyperemia;
- violation of the functional state;
- hyperthermia (rise in temperature).
Stages 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 vasodilation in the zone of direct traumatization. There is an increase in the permeability of their walls and an increase in local microcirculation. Humoral defense cells come here along with the blood flow.
In the second stage, immune cells begin to fight microorganisms that are at the site of damage. A process called phagocytosis begins. Neutrophil cells change their shape and absorb pathological agents. Further, special substances are released, aimed at the destruction of 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. Hearthinflammation, as it were, is protected from the whole organism. Sometimes a pulsation can be felt in this place. Cellular mediators of inflammation begin to be produced by mast cells, which allows you to cleanse the injured area of toxins, toxins and other substances.
General concepts of mediators
Mediators of inflammation are active substances of biological origin, the release of which is accompanied by the main phases of alteration. They are responsible for the occurrence of manifestations of inflammatory reactions. For example, an increase in the permeability of the walls of blood vessels or a local increase in temperature in the area of injury.
The main mediators of inflammation are released not only during the development of the pathological process. Their development is ongoing. It is aimed at regulating body functions at the tissue and cellular levels. Depending on the direction of action, modulators have an effect:
- additive (additional);
- synergetic (potentiating);
- antagonistic (weakening).
When damage occurs or at the site of action of microorganisms, the mediator link controls the processes of interaction of inflammatory effectors and the change in the characteristic phases of the process.
Types of inflammatory mediators
All inflammatory modulators are divided into two large groups, depending on their origin:
- Humoral: kinins, complement derivatives, blood coagulation factors.
- Cellular: vasoactive amines, arachidonic acid derivatives, cytokines, lymphokines,lysosomal factors, reactive oxygen metabolites, neuropeptides.
Humoral inflammatory mediators are in the human body before the impact of the pathological factor, that is, the body has a supply of these substances. Their deposition occurs in cells in an inactive form.
Vasoactive amines, neuropeptides and lysosomal factors are also preexisting modulators. The remaining substances belonging to the group of cellular mediators are produced directly during the development of the inflammatory response.
Complement derivatives
Inflammatory mediators include compliment derivatives. This group of biologically active substances is considered the most important among humoral modulators. Derivatives include 22 different proteins, the formation of which occurs during complement activation (the formation of an immune complex or immunoglobulins).
- Modulators C5a and C3a are responsible for the acute phase of inflammation and are histamine liberators produced by mast cells. Their action is aimed at increasing the level of vascular cell permeability, which is carried out directly or indirectly through histamine.
- Modulator C5a des Arg increases the permeability of venules at the site of the inflammatory reaction and attracts neutrophil cells.
- C3b promotes phagocytosis.
- C5b-C9 complex is responsible for the lysis of microorganisms and pathological cells.
This group of mediators is produced from plasma and tissue fluid. Thanks to admission topathological zone, exudation processes occur. Complement derivatives release interleukins, neurotransmitters, leukotrienes, prostaglandins and platelet activating factors.
Kinins
This group of substances are vasodilators. They are formed in tissue fluid and plasma from specific globulins. The main representatives of the group are bradykinin and kallidin, the effect of which is manifested as follows:
- participate in the contraction of the muscles of smooth groups;
- by reducing the vascular endothelium, they increase the processes of wall permeability;
- help increase blood and venous pressure;
- expand small vessels;
- cause pain and itching;
- help accelerate regeneration and collagen synthesis.
The action of bradykinin is aimed at opening the access of blood plasma to the focus of inflammation. Kinins are inflammatory pain mediators. They irritate local receptors, causing discomfort, pain, itching.
Prostaglandins
Prostaglandins are cellular mediators of inflammation. This group of substances belongs to the derivatives of arachidonic acid. The sources of prostaglandins are macrophages, platelets, granulocytes and monocytes.
Prostaglandins are inflammatory mediators with the following activity:
- irritation of pain receptors;
- vasodilation;
- increase in exudative processes;
- gainhyperthermia in the lesion;
- acceleration of the movement of leukocytes to the pathological zone;
- increased puffiness.
Leukotrienes
Biologically active substances related to newly formed mediators. That is, in the body in a state of rest of the immune system, their number is not enough for an immediate response to an irritating factor.
Leukotrienes provoke an increase in the permeability of the vascular wall and open access for leukocytes to the pathology zone. They are important in the genesis of inflammatory pain. Substances are capable of being synthesized in all blood cells, except for erythrocytes, as well as in the adventitia of lung cells, blood vessels and mast cells.
In the case of an inflammatory process in response to bacteria, viruses or allergic factors, leukotrienes cause bronchospasm, provoking the development of swelling. The effect is similar to the action of histamine, but longer. The target organ for active substances is the heart. Being released in large quantities, they act on the heart muscle, slow down coronary blood flow and increase the level of the inflammatory response.
Thromboxanes
This group of active modulators is formed in the tissues of the spleen, brain cells, lungs and blood cells, platelets. They have a spastic effect on blood vessels, enhance the processes of thrombus formation during cardiac ischemia, promote the processes of platelet aggregation and adhesion.
Biogenic amines
The primary mediators of inflammation are histamine and serotonin. Substances are provocateurs of initial disturbances of microcirculation in the area of pathology. Serotonin is a neurotransmitter 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 number increases sharply. Serotonin becomes a vasodilator, increasing the permeability of the vascular wall and dilating the vessels. Moreover, its action is a hundred times more effective than the second neurotransmitter of biogenic amines.
Histamine is an inflammatory mediator that has a versatile effect on blood vessels and cells. Acting on one group of histamine-sensitive receptors, the substance dilates the arteries and inhibits the movement of leukocytes. When exposed to another, it narrows the veins, causes an increase in intracapillary pressure and, conversely, stimulates the movement of leukocytes.
Acting on neutrophil receptors, histamine limits their functionality, on monocyte receptors - stimulates the latter. Thus, the neurotransmitter can have an inflammatory anti-inflammatory effect at the same time.
The vasodilating effect of histamine is enhanced by a 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, cell damage and death. Proteinases, which are the maina component of lysosomal enzymes, have the action of antimicrobial protection, lysing foreign destroyed pathological microorganisms.
In addition, active substances increase the permeability of the vascular walls, modulate the infiltration of leukocytes. Depending on the amount of enzymes released, they can enhance or weaken the migration of leukocyte cells.
The inflammatory response develops and persists for a long time due to the fact that lysosomal enzymes activate the complement system, release cytokines and lymokines, activate coagulation and fibrinolysis.
Cationic proteins
Inflammatory mediators include proteins contained in neutrophilic granules and having high microbicidal activity. These substances act directly on the foreign cell, violating its structural membrane. This causes the death of the pathological agent. Next comes the process of destruction and cleavage by lysosomal proteinases.
Cationic proteins promote the release of the neurotransmitter histamine, increase vascular permeability, accelerate 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 vascular wall permeability. They also stimulate leukocyte cells tokilling, absorption and destruction of alien settled microorganisms, enhance the process of phagocytosis.
After the killing of pathological agents, cytokines stimulate the restoration and proliferation of new cells. Substances interact with representatives from their group of mediators, prostaglandins, neuropeptides.
Reactive Oxygen Metabolites
A group of free radicals, which, 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 mediators include:
- hydroxyl radical;
- hydroperoxide radical;
- superoxide anion radical.
The source of these active substances is the outer layer of arachidonic acid, the phagocytic explosion when stimulated, and the oxidation of small molecules.
Oxygen metabolites increase the ability of phagocytic cells to destroy foreign agents, cause fat oxidation, damage to amino acids, nucleic acids, carbohydrates, which increases vascular permeability. As modulators, metabolites are able to increase inflammation or have an anti-inflammatory effect. They are of great importance in the development of chronic diseases.
Neuropeptides
This group includes calcitonin, neurokinin A and substance P. These are the best known neuropeptide modulators. The effect of substances is based onfollowing processes:
- attraction of neutrophils to the focus of inflammation;
- increased vascular permeability;
- help with the impact of other groups of neurotransmitters on sensitive receptors;
- increased sensitivity of neutrophils to venous endothelium;
- participation in the formation of pain during the inflammatory response.
In addition to all of the above, active mediators also include acetylcholine, adrenaline and norepinephrine. Acetylcholine takes part in the formation of arterial hyperemia, dilates blood vessels in the focus of pathology.
Norepinephrine and epinephrine act as modulators of inflammation, inhibiting the growth of vascular permeability.
The development of an inflammatory response is not a violation of the body. On the contrary, it is an indicator that the immune system is coping with its tasks.
