This document discusses chemical mediators of inflammation. It describes how mediators are generated from cells or plasma proteins and act on blood vessels, inflammatory cells, or other cells. Mediators are classified as cell-derived preformed, newly synthesized, or plasma-derived. Examples of mediators discussed include histamine, serotonin, arachidonic acid metabolites, lysosomal components, cytokines, free radicals, and products of the kinin, clotting, fibrinolytic, and complement systems. The document also briefly outlines how mediators regulate inflammation and cellular protection factors.

1. Dr. SANDHYA
DEPT OF PERIODONTICS
AND ORAL IMPLANTOLOGY
GOVT DENTAL COLLEGE
CHENNAI

2. CONTENTS
Introduction
Properties &General principles
Classification
Cell derived inflammatory mediators
Plasma derived inflammatory mediators
Conclusion

5. CHEMICAL MEDIATORS
• Any messenger that acts on blood vessels,
inflammatory cells, or other cells to contribute
to an inflammatory response.

6. GENERAL PRINCIPLES
 Mediators are generated either from cells or
from plasma proteins
 Active mediators are produced in response to
various stimuli
 One mediator can stimulate the release of other
mediators
 Mediators vary in their range of cellular targets
 Once activated &released from the cell, most of
these are short lived

7. CLASSIFICATION
MEDIATORS OF
INFLAMMATION
CELL DERIVED
PREFORMED
NEWLY
SYNTHESISED
PLASMA
DERIVED
INACTIVE
PRECURSORS

9. VASOACTIVE AMINES
HISTAMINE:
First mediators to be released
Present in mast cells, blood basophils and
platelets.
MAST CELL
DEGRANULATION
PHYSICAL
INJURY
ALLERGIC
REACTIONS
ANAPHYLATOXINS
(C3a AND C5a)
NEUROPEPTIDES
(SUBSTANCE P)
CYTOKINES(IL-
1,IL-8)

10. ACTIONS OF HISTAMINE
DIRECT
INDIRECT
Vasodilatation
Increased vascular
permeability
Itching
Pain
Increases the
inflammatory
response
Causes the release of
cytokines and other
inflammatory mediators
 Increase in salivary histamine levels is correlated with
the severityof periodontitis (Venza et al2006)

11. 46
Dilation of arterioles
Permeability of
vasculature

12. SEROTONIN(5-HYDROXYTRYPTAMINE):
 Derived from chromaffin cells of GIT, spleen,
nervous tissue, mast cells, platelets
 Release is triggered by platelet aggregation to
collagen ,thrombin, ADP ,antigen-antibody
complexes.
 Actions are similar to histamine but less potent

13. ARACHIDONIC ACID METABOLITES
• CYCLO-OXYGENASE PATHWAY
ACTIVATED ARACHIDONIC ACID
PGG2 PGH2
Inhibits the
proinflammat
ory cytokines
•Vasodilator
•Bronchodilat
or
•Anti-
aggregating
•Vasoconstri
ctor
•Bronchocon
strictor
•Platelet
aggregation
•Vasodilator
•Bronchocons
trictor
PGD2,PGE2
•Vasodilator
•Bronchodilat
or
•Increases
permeability
FREE OXYGEN RADICAL
PGF2-α TXA2 PGI2 RESOLVINS
CYCLO-OXYGENASE

14. •LIPO-OXYGENASE PATHWAY
ACTIVATED ARACHIDONIC ACID
5-HPETE
LTA4
5-HETE
CHEMOTACTIC
•CHEMOTACTIC
•CELL ADHERENCE
•SMOOTH MUSCLE CONSTRICTOR
•VASOCONSTRICTOR
•BRONCHOCONSTRICTOR
•INCREASED VASCULAR PERMEABILITY
LTB4 LTC4 LTD4 LTE4 LIPOXINS
LIPO-OXYGENASE

15. LYSOSOMAL COMPONENTS
GRANULES OF NEUTROPHILS

16. PLATELET ACTIVATING FACTOR
Released by Ig-E sensitised basophils and
mast cells,leucocytes ,endothelium,platelets.
Actions
• Vasodilator
• Bronchoconstrictor
• Increases permeability
• Adhesion of leucocyte to endothelium
• chemotaxis

18. CYTOKINES
 ACUTE INFLAMMATION-
1. Tumor Necrosis Factor(TNF)
2. Interleukin-1(IL-1)
3. IL-6
 CHRONIC INFLAMMATION-
1. IL-12
2. IL-17
3. IFN
 CHEMOKINES- IL-8,MCP-1,Eotaxin etc,.
• IL-8,IL-6,IL-1- Mainly involved in inflammation of dental
pulp.

19. Microbial products ,other cytokines,toxins
Activation of macrophages
TNF/IL-1
•Expression of
leukocyte adhesion
molecules
• Procoagulant
• Anticoagulant
activity
•Activation
•Production of
cytokines
•Proliferation
•Increased
collagen
synthesis
•Fever
•Leukocytosis
•Increased
APRs
•Decreased
appetite
•Increased
sleep
INFLAMMATION REPAIR
SYSTEMIC
MANIFESTATION
OF
INFLAMMATION
LOCAL EFFECTS SYSTEMIC EFFECTS
VASCULAR ENDOTHELIUM LEUKOCYTES FIBROBLASTS

20. FREE RADICALS
 REACTIVE OXYGEN SPECIES
 Released extracellularly from leukocytes
 Superoxide anion , hydrogen peroxide and hydroxyl radical.
 They cause endothelial damage, injury to other cells
,inactivation of anti-protease.
 NITRIC OXIDE
 Endothelium derived relaxing factor
 Acts by induction of cyclic GMP and causes relaxation of
vascular smooth muscles.
 Inhibitor of cellular changes of inflammation.

21. PLASMA PROTEIN-DERIVED
MEDIATORS
• Products derived from the activation of 4
interlinked systems
KININ
SYSTEM
CLOTTING
SYSTEM
FIBRINOLYTIC
SYSTEM
COMPLEMENT
SYSTEM
PLASMA PROTEIN
DERIVED
MEDIATORS

22. KININ SYSTEM

23. CLOTTING SYSTEM

24. FIBRINOLYTIC SYSTEM

25. 53
FACTOR XII
FACTOR XIIa
FIBRINOLYTIC
SYSTEM
CLOTTING
SYSTEM KININ SYSTEM
PLASMIN FIBRIN BRADYKININ
COMPLEMENT SYSTEM
C3a , C5a
INTER-RELATIONSHIP

26. COMPLEMENT SYSTEM

27. ACTIONS OF ACTIVATED COMPLEMENT
SYSTEM
C3a,C5a,C4a(anaphylatoxins)-release of
histamine.
C3b is a opsonin
C5a is chemotactic
Membrane attack complex -MAC(C5b to C9)-
holes in phospholipid membrane of the cell.

28. REGULATION OF INFLAMMATION

29. Acute phase reactants
Corticosteroids
Free cytokine receptors
Anti-inflammatory chemical mediators
CELLULAR
PROTECTION
FACTORS
COAGULATION
PROTEINS
ANTIOXIDANTS
STRESS
PROTEINS
C-REACTIVE
PROTEINS