Classification by origin
All mediators or their precursors are synthesized within the body's cells. Depending on the mode of activation, they are divided into two large groups:
- Cellular mediators. Formed inside cells and accumulated there in an already activated state. When inflammation develops, they are released into the lesion ready for action.
- Plasma (humoral) mediators. They are also synthesized by cells, but enter blood plasma or intercellular fluid in an inactive form. Their activation occurs strictly on-site — directly in the focus of inflammation.
Cellular inflammatory mediators
This is the most extensive group of substances, determining the dynamics of local reactions. Key classes:
- Biogenic amines. Histamine (from mast cells and basophils) acts in a dose-dependent manner: in low doses via H₁ receptors it causes pain and pruritus, while in high doses via H₂ receptors it increases vascular permeability and stimulates leukocyte migration. Serotonin causes venous hyperemia and activates thrombus formation.
- Lipid derivatives. Synthesized from cell membrane phospholipids (arachidonic acid). Prostaglandins are formed via the cyclooxygenase pathway, and leukotrienes, which cause prolonged microvessel spasm, via the lipoxygenase pathway. This group also includes platelet-activating factor, a potent spasmogen.
- Neurotransmitters. Catecholamines (adrenaline, noradrenaline) constrict arterioles, causing ischemia, and activate metabolism. Acetylcholine dilates blood vessels, leading to arterial hyperemia. Substance P induces cytokine production by macrophages.
- Peptides and proteins. Cytokines (interleukins, interferons, growth factors) regulate target cells. Leukokinins stimulate the production of acute-phase proteins (C-reactive protein, haptoglobin, ceruloplasmin), whose elevation indicates an acute process. Enzymes (hydrolases, lyases) participate in all stages of inflammation.
- Nucleotides and nitric oxide (NO). ATP provides energy to cells, ADP stimulates thrombus formation and sludge phenomenon, and adenosine causes vasodilation. Nitric oxide acts as a potent vasodilator and exhibits cytotoxicity by binding iron ions.
Plasma inflammatory mediators
This group is represented by three interconnected blood protein systems:
- Kinin system (bradykinin, kallidin).
- Complement system proteins (including the C3 fraction, which also belongs to acute-phase proteins).
- Hemostasis system factors (procoagulants, anticoagulants, and fibrinolysis components).
Plasma factors determine the outcomes of inflammation and shape its systemic and local manifestations.
Role of mediators in pathogenesis
Mediators are the true "engine of inflammation". Without them, the process could not develop regularly. Their main functions:
- Initiation and regulation of alternation (tissue damage).
- Ensuring vascular reactions (succession of ischemia, arterial, and venous hyperemia).
- Control of exudation (fluid leakage into tissues).
- Regulation of leukocyte emigration into the lesion and stimulation of phagocytosis.
- Initiation of tissue repair processes (proliferation).
Briefly: answers to topical questions
What effects do kinins cause in inflammation?
Kinins (bradykinin, kallidin) cause the following effects in inflammation:
- increased microvascular permeability;
- arteriolar dilation;
- pain;
- activation of Hageman factor;
- stimulation of phagocyte chemotaxis;
- activation of collagenogenesis and cyclooxygenase.
For bradykinin, the following are also indicated:
- vasodilation with a decrease in blood pressure;
- increased permeability with exudation and inflammation;
- interaction with nociceptors to induce pain;
- promotion of pro-inflammatory mediator formation, primarily histamine;
- natriuresis and diuresis.
Which complement system factors act as inflammatory mediators?
The following complement system components and their fragments act as inflammatory mediators:
- C3a and C5a are anaphylatoxins that stimulate histamine release from mast cells, leading to smooth muscle contraction and increased vascular permeability;
- C5a is a potent chemoattractant that activates cell chemotaxis toward the focus of inflammation;
- C3b acts as an opsonin that enhances phagocytosis by macrophages and neutrophils;
- Complement fraction C3 belongs to the acute-phase proteins of inflammation.
Which mediators cause arterial hyperemia in inflammation?
The development of arterial hyperemia in inflammation is caused by the formation and action of vasoactive substances—inflammatory mediators.
Mediators and substances with vasodilator action confirmed by sources include:
- acetylcholine — reduces the tone of arteriolar smooth muscle cells, dilates the arteriolar lumen, and causes arterial hyperemia;
- kinins, including bradykinin and kallidin — dilate arterioles;
- adenosine — exerts a vasodilator effect accompanied by the development of arterial hyperemia;
- prostaglandins, including groups E and I, e.g., prostacyclin — dilate arterioles/microvessels;
- nitric oxide (NO) — a potent vasodilator;
- histamine — dilates arterioles.
Which substances are acute-phase proteins of inflammation?
Acute-phase proteins (markers of acute inflammation) include the following substances:
- C-reactive protein (CRP);
- Haptoglobin;
- Ceruloplasmin;
- Plasminogen;
- Transferrin;
- α₁-antitrypsin;
- Antithrombin III;
- Complement component 3 (C3 fraction);
- Fibrinogen;
- α₂-macroglobulin.
To easily remember the three plasma mediator systems, use the mnemonic KGB: Kinins, Hemostasis (Coagulation), Complement proteins.
Class and exam questions
What is the difference between cellular and plasma mediators?
Cellular mediators are released into the focus of inflammation already in their active form. Plasma mediators enter tissues in an inactive state and are activated only at the site of injury.
What effects does histamine cause in inflammation?
In low doses (via H₁ receptors), it causes pain, burning, and pruritus. In high concentrations (via H₂ receptors), it increases venule permeability, stimulates leukocyte migration, and the synthesis of other mediators.
What are acute-phase proteins?
These are markers of acute inflammation (C-reactive protein, haptoglobin, transferrin, etc.), the production of which is stimulated by leukokines. Their elevated blood levels indicate an active acute process.
How do catecholamines act in the focus of inflammation?
Adrenaline and noradrenaline cause contraction of arteriolar smooth muscle cells. This leads to a decrease in their lumen and the development of tissue ischemia.
What else to study on this topic
- Arachidonic acid metabolism: cyclooxygenase and lipoxygenase pathways
- Mechanisms of cytotoxic action of nitric oxide (NO)
- Role of nucleotides (ATP, ADP, adenosine) in microcirculation regulation
- Lipid peroxidation (LPO) processes in health and disease
- Involvement of enzymes (hydrolases, oxidoreductases) in alteration processes
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