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.
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
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)
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
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
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.