Inflammation and anti-inflammatory drugs

Question 1

Name the 3 main cytokines/mediators involved in the late phase of inflammation and briefly describe their function

Answer 1

These are involved in degradation of the damaged tissue and preparation of the site of injury for healing

IL-1 and TNF are produced by activated neutrophils and macrophages

Leukocyte production of proteolytic enzymes and oxygen radicals leads to degradation

Question 2

Describe the systemic effects of the cytokines released in response to injury/infection

Answer 2

There are specific cytokine receptors in hypothalamus which result in :

Increased level of corticosteroids to promote short term inflammations

Increased hepatic acute phase proteins

Stimulates bone marrow to produce more leukocytes

Question 3

Describe the granulation phase (4-21 days post injury)

Answer 3

Macrophages and platelets produce growth factors which are involved in fibroblast proliferation, angiogenesis (blood vessel formation) and collagen synthesis

Question 4

Granulomatous conditions such as rheumatoid arthritis and scleroderma are caused by

Answer 4

Failure to stop the proliferative/granulation phase

Question 5

Describe the impact of sex hormones on the proliferation/granulation phase

Answer 5

Oestrogen promotes and speeds up healing , testosterone prolongs the healing process

Question 6

Describe the maturation phase (21 days - 2 years post injury)

Answer 6

Cessation of proliferative phase,

Reduced vascularisation

Remodelling of collagen

Reinnervation

Lack of elastin causes scar tissue

Question 7

Function of phospholipase A2

Answer 7

Converts phosphotidylcholine (cell membrane phospholipids) to arachidonic acid

Arachidonic acid can activated enzymes involved in inflammation, pain and fever (COX-2 and lipoxygenase)

Question 8

Contrast and compare the action of aspirin and Indomethacin (and other NSAIDS)

Answer 8

Aspirin is a non-competitive irreversible inhibitor of cyclooxygenase

Indomethacin and other NSAIDS are competitive reversible inhibitors of COX enzymes ; both are non-selective for the different isoform of COX

Question 9

What does NSAIDs mean

Answer 9

Non-steroidal anti-inflammatory drugs

Question 10

Describe the action of NSAIDs

Answer 10

Competitive inhibitors of cyclooxygenase result in suppression of prostaglandin synthesis.

Also reduced expression of adhesion molecules that allow the migration of leukocytes to site of inflammation

Question 11

Describe the action of glucocorticoids

Answer 11

These acts as a long term treatment to inhibit inflammation

in short term they increase inflammatory response

They reduce:

• Prostanoid and leukotriene production (both are prostaglandins)
• expression of cell adhesion molecules
• chemotaxis of neutrophils
• cytokine production

They increase action of vasoconstrictors