Inflammation
Mediators
Histamine
Bradykinin
Eicosanoid
prostaglandins PGE
leukotrienes
Neuropeptides
Substance P
Nitric oxide
Cytokines + Chemokines
Cytokines
Interleukin -1
Complement Pathway
e.g. C3a, C5a
Microcirculation
Arteriole
increased bloo flow due to inflamation
Venule
cell accumulation
oedema formation
Vasodilators: prostaglandins nitric oxygen Neuropeptides (e.g. CGRP)
source: endothelial cells inflammatory cells
sensory nerves
due to plasma extravasation
= inflammatory swelling
oedema producing mediators
neutrophil dependent: agents that stimulate Neutrophil activation
Direct acting:
Histamine
substance P
bradykinin
PAF (platelet activating factor)
Leukotrienes
Mediators leading to neutrophil accumulation in tissue
- Neutrophil acitvating agents:
LTB4 (Leukotrien)
C5a
IL-8
- Endothelial adhesion molecule stimulants:
TNF and IL-1
major source: mast cells, basophils
allergic/ hypersensitivity responses
hay fever
allegy
skin irritation
H1 receptor
increases blood flow
increased microvascular permeability
itch
H1 antagonists
Chlorpheniramine
non-sedating
terfenadine
cetirizine
astemizole
metabolised by ACE + carboxypeptidase
peptide formed in plasma by activity
of enzymes on kininogens (tissue fluid substrates)
B-2 receptors
increase blood flow
increase micorvascular permeability
nociception
broncho-constriction
nasal blockage (present in nasal cavity druing allergic rhinitic attakcs
B-2 antagonists
inhibit effect of some angioedemas
B-1 receptors
induced in inflammation
mediate pain
mediators of mast cell activation
influence anaphylactic shock
activated by
Immune complexes Mircrobes
pathogens on cell surface
mediate uptake of phagocytes
mediate lysis of pathogens and cells
vasodilators
increase pain sensation
induce fever
increase oedema formation
some are broncho-constrictors
Cyclo-oxygenase pathway from arachidonic acid
lipoxygenase pathway from arachidonic acid
TNF-alpha
arthritis
synergistically influence each other
peptides/proteins
secreted by inflammatory cells
pleiotrophic
= more than one effect
can be pro- and antiinflammatory
can cause cytokine storm
can act synergistically
or antagonise each other
potent effects in small amounts
act on specific receptors
Tumor necrosis factor
huge role in chronic inflammation
stimulation of emigration of inflammatory cells
e.g. neutrophils and macrophages
sectretion of other cytokines
IL-1
IL-6
IL-17
pro-inflammatory
IL-2
t-cell acitvation
IL-3
bone marrow stimulant
IL-5
eosinophil activation
IL-10
IL-4
anti-inflamatory
Chemokines
= smaller peptides
bind to G-protein coupled receptors
Inhibitors (Antibodies)