Dr.

SANDHYA
DEPT OF PERIODONTICS
AND ORAL IMPLANTOLOGY
 CONTENTS
 Introduction

 Properties & General principles

 Classification

 Cell derived inflammatory mediators

 Plasma derived inflammatory mediators

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

MEDIATORS OF
INFLAMMATION

PLASMA
CELL DERIVED
DERIVED

NEWLY INACTIVE
PREFORMED
SYNTHESISED PRECURSORS
 VASOACTIVE AMINES
HISTAMINE:
First mediators to be released
Present in mast cells, blood basophils and
platelets.

MAST CELL
DEGRANULATION

PHYSICAL ALLERGIC ANAPHYLATOXINS NEUROPEPTIDES CYTOKINES(IL-

INJURY REACTIONS (C3a AND C5a) (SUBSTANCE P) 1,IL-8)
 ACTIONS OF HISTAMINE
DIRECT
INDIRECT

Vasodilatation
Causes the release of
cytokines and other
inflammatory mediators
Increased vascular
permeability Increases the
inflammatory
response
Itching

Pain

 Increase in salivary histamine levels is correlated with

the severityof periodontitis (Venza et al2006)
 Dilation of arterioles

Permeability of
vasculature

46
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

 ARACHIDONIC ACID METABOLITES
• CYCLO-OXYGENASE PATHWAY
ACTIVATED ARACHIDONIC ACID

CYCLO-OXYGENASE

PGG2 PGH2 FREE OXYGEN RADICAL

PGF2-α TXA2 PGI2 RESOLVINS

PGD2,PGE2
•Vasoconstri •Vasodilator
•Vasodilator •Vasodilator Inhibits the
ctor •Bronchodilat
•Bronchodilat •Bronchocons proinflammat
•Bronchocon or
or trictor ory cytokines
strictor •Anti-
•Increases aggregating
•Platelet
permeability
aggregation
•LIPO-OXYGENASE PATHWAY
ACTIVATED ARACHIDONIC ACID

LIPO-OXYGENASE
5-HETE
5-HPETE
CHEMOTACTIC

LTA4

LTB4 LTC4 LTD4 LTE4 LIPOXINS

•SMOOTH MUSCLE CONSTRICTOR
•CHEMOTACTIC •VASOCONSTRICTOR
•CELL ADHERENCE •BRONCHOCONSTRICTOR
•INCREASED VASCULAR PERMEABILITY
 LYSOSOMAL COMPONENTS
GRANULES OF NEUTROPHILS
 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
 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.
 Microbial products ,other cytokines,toxins

Activation of macrophages

TNF/IL-1

LOCAL EFFECTS SYSTEMIC EFFECTS

VASCULAR ENDOTHELIUM LEUKOCYTES FIBROBLASTS •Fever

•Leukocytosis
•Expression of •Increased
leukocyte adhesion •Proliferation
•Activation •Increased APRs
molecules •Production of •Decreased
• Procoagulant collagen
cytokines appetite
• Anticoagulant synthesis
•Increased
activity sleep

SYSTEMIC
MANIFESTATION
INFLAMMATION REPAIR OF
INFLAMMATION
 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.
 PLASMA PROTEIN-DERIVED
MEDIATORS
• Products derived from the activation of 4
interlinked systems

KININ CLOTTING
SYSTEM SYSTEM

PLASMA PROTEIN
DERIVED
MEDIATORS

FIBRINOLYTIC COMPLEMENT
SYSTEM SYSTEM
KININ SYSTEM
CLOTTING SYSTEM
FIBRINOLYTIC SYSTEM
 INTER-RELATIONSHIP
FACTOR XII

FACTOR XIIa

FIBRINOLYTIC CLOTTING
SYSTEM SYSTEM KININ SYSTEM

PLASMIN FIBRIN BRADYKININ

COMPLEMENT SYSTEM

C3a , C5a
53
COMPLEMENT SYSTEM
 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.
REGULATION OF INFLAMMATION
Acute phase reactants
CELLULAR
PROTECTION
FACTORS

C-REACTIVE COAGULATION
PROTEINS PROTEINS

STRESS
ANTIOXIDANTS
PROTEINS

Corticosteroids

Free cytokine receptors

Anti-inflammatory chemical mediators