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

  1. Neutrophil acitvating agents:
    LTB4 (Leukotrien)
    C5a
    IL-8
  1. 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)