Inflammatory mediators are the substances that initiate and regulate inflammatory reactions. Many mediators have been identified and targeted therapeutically to limit inflammation.

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CHEMICAL
MEDIATORS
OF INFLAMATION
VASOACTIVEAMINES
ARACHIDONIC ACIDMETABOLITES
Abhinav S
2nd year MBBS
Government Medical College
Thiruvallur, Tamil Nadu

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CONTENTS
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INFLAMMATION
MEDIATORS OF INFLAMMATION
GENERAL FEATURES
MAIN CHEMICAL MEDIATORS OF ACUTE INFLAMMATION
CELL-DERIVED MEDIATORS
• Vasoactive Amines
• ARACHIDONIC ACID METABOLITES
• A. Products of cyclooxygenase pathway
• B. Products of lipoxygenase pathway:
FLOW CHART

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What is
INFLAMMATION ?
•Inflammation is a response of vascularized
tissues that delivers leukocytes and
molecules of host defense from the
circulation to the sites of infection and cell
damage in order to eliminate the offending
agents
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MEDIATORS OF
INFLAMMATION
•Inflammatory mediators are the substances
that initiate and regulate inflammatory
reactions.
• Many mediators have been identified and
targeted therapeutically to limit
inflammation.
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GENERAL
FEATURES OF
CHEMICAL
MEDIATORS
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• SOURCE OF MEDIATORS
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CELL-DERIVED MEDIATORS PLASMA DERIVED
• Present either as preformed molecules
(e.g. histamine In mast cell granules)
or are synthesized de novo (e.g.
prostaglandins, cytokines) in response
to a stimulus
• Produced usually by platelets,
neutrophils, monocytes/macrophages,
and mast cells.
• Plasma-derived mediators: Produced
mainly in the liver and present in the
circulation as inactive precursors,
which require activation (e.g.
complement proteins, kinins)

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• TIGHTLY REGULATED
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• INTER-RELATED :-
• Most act by binding to
specific receptor on
target cells
One mediator can stimulate the release of other
mediators. The secondary mediators may have the
similar, different or even opposite actions

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• Diverse targets:
• Short-lived: Most of these mediators
have a short- lifespan
Target cell type varies depending on the type of mediator. They can act
on one or few or many diverse targets, or may have different effects on
different types of cells

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MAIN CHEMICAL MEDIATORS OF
ACUTE INFLAMMATION

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CELL-DERIVEDMEDIATORS
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Vasoactive Amines: Histamine and Serotonin
Histamine and serotonin are the first mediators to be
released during inflammation, which are stored as
preformed molecules in cells.

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It is a preformed vasoactive mediator. Responsible for immediate transient response.
Source:
Mast cells (richest source), blood basophils
and platelets.
Stimuli:
– Physical injury (e.g. trauma, cold, heat)
– Immune reactions in which antibodies bind to mast cells (e.g. allergic reactions)
– Other chemical mediators: C3a and C5a, leukocyte-derived histamine-releasing proteins, neuropeptides
(e.g. substance P), cytokines (IL-1, IL-8).
Actions:
(1) Dilation of arterioles
(2) increase of the vascular permeability. 12
1. Histamine

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It is a preformed vasoactive mediator
 Source: Platelets, some neurons and enterochromaffin cells in the
gastrointestinal tract.
 Stimulus: Platelet aggregation and antigen-antibody complexes.
 Actions: Similar to those of histamine.
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2. Serotonin
(5-hydroxytryptamine
vasoactive mediator)

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ARACHIDONIC ACID
METABOLITES
PROSTAGLANDINS
LEUKOTRIENES
LIPOXINS

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ARACHIDONIC ACID (A A)
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Arachidonic acid: Can be enzymatically
converted into
prostaglandins and leukotrienes (both together
called as eicosanoids).
Source: Derived from cell membrane phospholipids mainly by the enzyme
phospholipase A2.
Stimuli: Mechanical, chemical, and physical stimuli or other mediators (e.g. C5a).
AAmetabolism: Occurs along two major enzymatic pathways These are
cyclooxygenase pathway (produce prostaglandins) and lipoxygenase pathway
(produces leukotrienes and lipoxins).

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A.Productsof
cyclooxygenasepathway:
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Products: Most important in inflammation are PGE2, PGD2, PGI2 (prostacyclin), and TXA2
(thromboxane A2).
Mechanism: They are produced from AA by the actions of two cyclooxygenases, COX-1
and COX-2.
 Local effects:
– TxA2: Vasoconstriction and promotes platelet aggregation
– Prostacyclin (PGI2): Vasodilator and inhibits platelet aggregation
– PGD2 and PGE2: Vasodilation and increased permeability. PGD2 is also a
chemoattractant for neutrophils.
 Systemic effects:
– Prostaglandins are responsible for pain and fever in inflammation.
– PGE2 causes cytokine-induced fever during infections.

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B.Productsof
lipoxygenasepathway:
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(1) Leukotrienes
(2) lipoxins.
1. Leukotrienes: Products and their actions:
 5-hydroxyeicosatetraenoic acid (5-HETE): Chemotactic for neutrophils, and is the
precursor of the leukotrienes.
 LTB4
• Chemotactic agent
• Neutrophil activation causing adhesion to endothelium, generation of ROS, and release
of lysosomal enzymes.
 Leukotrienes C4, D4, and E4(LTC4, LTD4, LTE4)
• Vasoconstriction
• Bronchospasm (in asthma)
• Increased vascular permeability.

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2. Lipoxins (LXs):
• Actions: Inhibit inflammation
– Inhibit neutrophil chemotaxis and recruitment.
– Inhibit leukocyte adhesion to endothelium.

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Thank You 1
ANY
QUESTIONS
?

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“Dive into books,
find your answers.”

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REFERENCE

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Thank
You