Inflammatory mediators are biologically active substances generated during tissue injury. They act as the primary "engine" of pathogenesis, driving the orderly development of the process and shaping all local and systemic signs of inflammation.
NatureBiologically active substances (BAS)
ClassificationCellular (active) and plasma (inactive)
Primary roleEngine of inflammation from onset to resolution
All mediators or their precursors are synthesized by the body's cells. Depending on the mode of activation, they are divided into two major groups:
Cellular mediators. Formed intracellularly and stored there in an already active state. When inflammation develops, they are released into the lesion ready for action.
Plasma (humoral) mediators. Also synthesized by cells, but released into blood plasma or extracellular fluid in an inactive form. Their activation occurs strictly on-site — directly within the focus of inflammation.
Cellular Inflammatory Mediators
This is the largest group of substances, determining the dynamics of local reactions. Key classes include:
Biogenic amines. Histamine (derived 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). The cyclooxygenase pathway generates prostaglandins, whereas the lipoxygenase pathway produces leukotrienes, which cause prolonged microvascular spasm. This group also includes platelet-activating factor (PAF), a potent spasmogen.
Neurotransmitters. Catecholamines (epinephrine, norepinephrine) constrict arterioles, causing ischemia, and stimulate metabolism. Acetylcholine dilates 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 points to an acute process. Enzymes (hydrolases, lyases) participate in all stages of inflammation.
Nucleotides and nitric oxide (NO). ATP provides cellular energy, ADP stimulates thrombus formation and the sludge phenomenon, while adenosine causes vasodilation. Nitric oxide acts as a potent vasodilator and exhibits cytotoxicity via iron-ion binding.
Plasma Inflammatory Mediators
This group is represented by three interrelated blood protein systems:
Kinin system (bradykinin, kallidin).
Complement system proteins (including the C3 fraction, which is also an acute-phase protein).
Hemostatic system factors (procoagulants, anticoagulants, and fibrinolytic 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 progress in an orderly fashion. Their main functions include:
Initiation and regulation of alteration (tissue damage).
Mediating vascular reactions (succession of ischemia, arterial hyperemia, and venous hyperemia).
Controlling exudation (fluid extravasation into tissues).
Managing leukocyte emigration into the lesion and stimulating phagocytosis.
To easily remember the three systems of plasma mediators, use the mnemonic KCF: Kinins, Complement proteins, Factors of hemostasis.
Frequently asked questions
What effects do kinins cause during inflammation?
Kinins (bradykinin, kallidin) cause the following effects during inflammation:
Increased microvascular permeability;
Arteriolar dilation;
Pain;
Activation of Hageman factor (Factor XII);
Stimulation of phagocyte chemotaxis;
Activation of collagenogenesis and cyclooxygenase.
Bradykinin specifically is also noted for:
Vasodilation with blood pressure reduction;
Increased permeability leading to exudation and inflammation;
Interaction with nociceptors to generate pain;
Promotion of pro-inflammatory mediator formation, primarily histamine;
Natriuresis and diuresis.
Which complement system factors act as inflammatory mediators?
The following complement components and their fragments act as inflammatory mediators:
C3a and C5a — anaphylatoxins that stimulate histamine release from mast cells, leading to smooth muscle contraction and increased vascular permeability;
C5a — a potent chemoattractant that drives cell chemotaxis toward the inflammatory focus;
C3b — acts as an opsonin, enhancing phagocytosis by macrophages and neutrophils;
The complement C3 fraction is also an acute-phase protein of inflammation.
Which mediators cause arterial hyperemia in inflammation?
The development of arterial hyperemia in inflammation is driven by the production and action of vasoactive substances — inflammatory mediators.
Confirmed mediator sources and substances with vasodilatory effects include:
Acetylcholine — decreases arteriolar smooth muscle tone, widens the arteriolar lumen, and causes arterial hyperemia;
Kinins, including bradykinin and kallidin — dilate arterioles;
Adenosine — exerts a vasodilatory effect accompanied by arterial hyperemia;
Prostaglandins, including groups E and I (e.g., prostacyclin) — dilate arterioles and microvessels;
Nitric oxide (NO) — a powerful vasodilator;
Histamine — dilates arterioles.
What substances are classified as acute-phase proteins of inflammation?
Acute-phase proteins (markers of acute inflammation) include:
C-reactive protein (CRP);
Haptoglobin;
Ceruloplasmin;
Plasminogen;
Transferrin;
α₁-Antitripsin;
Antithrombin III;
Complement C3 fraction;
Fibrinogen;
α₂-Macroglobulin.
How do cellular mediators differ from plasma mediators?
Cellular mediators are released into the inflammatory site already in an active form. Plasma mediators enter tissues in an inactive state and are activated only at the site of injury.
What effects does histamine cause during inflammation?
In low doses (via H₁ receptors), it causes pain, burning, and itching. In high concentrations (via H₂ receptors), it increases venular permeability, stimulates leukocyte migration, and promotes the synthesis of other mediators.
What are acute-phase proteins?
These are markers of acute inflammation (C-reactive protein, haptoglobin, transferrin, etc.) whose production is stimulated by leukokinins. Their high blood levels indicate an active acute process.
How do catecholamines act within an inflammatory lesion?
Epinephrine and norepinephrine cause contraction of arteriolar smooth muscle cells, reducing vessel lumen diameter and leading to tissue ischemia.
Go deeper
Arachidonic acid metabolism: cyclooxygenase and lipoxygenase pathways
Mechanisms of nitric oxide (NO) cytotoxic action
Role of nucleotides (ATP, ADP, adenosine) in microcirculation regulation
Lipid peroxidation (LPO) processes in health and pathology
Participation of enzymes (hydrolases, oxidoreductases) in alteration processes