7.2.1 Inflammation: Mediators and Targets

Question 1

What is acute inflammation and what are the 5 cardinal signs?

Answer 1

Immediate response to injury with short duration

• Rubor (redness)
• Calor (heat)
• Tumor (swelling)
• Dolor (pain)
• Functio laesa (loss of function)

Question 2

What is chronic inflammation and why does it occur?

Answer 2

On-going, repeat cycles, flare-up of inflammation.
- Stimulus not effectively removed
- Stimulus overwhelms system
- Stimulus by-passes immune response
- Lack of effective resolution and repair
- Immuno-suppressed

Question 3

What do mediators of inflammation do?

Answer 3

Required for resolution and repair following inflammatory insult. Cause vascular and cellular changes, inflammatory pain and pruritus in inflamed tissue.

Question 4

What are cytokines?

Answer 4

Peptides that work in medium-long term by inducing cellular changes. Druggable.
Released into circulation to cause acute phase proteins by liver and increase temp., blood flow, vascular permeability

Question 5

What are chemokines?

Answer 5

Chemoattractant cytokines that cause inflammatory cell recruitment.

Question 6

What mediators are stored in cells?

Answer 6

• Histamine
• Neuropeptides

Question 7

Where is histamine stored and how does it produce its effects?

Answer 7

Store in mast cells, platelets, basophils
Activates cell surface receptors
Mass histamine release = hypersensitivity and anaphylactic reaction

H1 receptor involved in inflammation

Question 8

Inflammatory mediators can be

Answer 8

Stored in cells
Synthesised by activated cells
Derived from precursors in plasma

Question 9

Give examples of mediators synthesised on cell activation

Answer 9

Lipid mediators:
- prostaglandins
- leukotrienes
- platelet activating factor (PAF)

Question 10

Describe the synthesis of prostaglandins

Answer 10

Cell activation -> phospholipase A2

Cell membrane phospholipid -P A2-> arachidonic acid

arachidonic acid -COX-> pGs and Tx

Question 11

Describe the actions of NSAIDs

Answer 11

Non-Steroidal Anti-Inflammatory Drugs
NSAIDs block the action of COX so prevents conversion of arachidonic acid to PGs and Tx

Question 12

Describe the synthesis of leukotrienes (LTs)

Answer 12

Arachidonic acid -(5-LO)-> LTs

Can be blocked experimentally

Question 13

Describe the actions of leukotriene D4 receptor antagonists

Answer 13

Zafirlukast (Accolate)
Monolukast (Sigulair)

Reduce bronchoconstriction
Asthma prophylaxis

Question 14

Describe the synthesis of platelet activation factor and what is its action?

Answer 14

Cell membrane phospholipid -lyso-PAF-> PAF

Platelet aggregation
Chemoattractant for leukocytes
Oxidative burst

Question 15

Give 5 examples of mediators derived from precursors in plasma

Answer 15

• Bradykinin (BK)
• Factors of the complement system (C5a)
• Opsinogens
• Chemoattractants
• Pore-forming complex

Question 16

What is bradykinin role and how is it inactivated?

Answer 16

Increases bloodflow = redness and heat
Sensitisation of sensory nerve endings = pain

Inactivated by ACE in lungs and kidney