Resolution to inflammation

Question 1

What are the steps of inflammation

Answer 1

Bee sting/ infection

Local release of inflammatory hormones

White blood cells from circulation transmigrate towards site of infection

Monocytes differentiate into macrophages

Acute inflammation

Question 2

What are treatments of acute inflammation?

Answer 2

Steroids

Anti-TNFa

NSAIDS

Question 3

What is resolution?

Answer 3

Active process

State caused by the removal of the inducible factors

Cause of inflammation are removed

Question 4

What are the requirements for reslution?

Answer 4

Clearance of stimulus

Chemokine catabolism

Decreased leukocyte trafficking

Apoptosis/ phagocytosis

Pro-resolution macrophages

Question 5

WHat happens if resolution does not happen correctly?

Answer 5

Break immune tolerance

Set the scene for autoimmunity and chronic inflammation

Question 6

What happens in failed resolution?

Answer 6

Bacteria not cleared

Grow and multiply

WBCs enter tissue

Stromal cells are angry and make more collagenous ECM = more granulomatose tissue

Chronic inflammation

Question 7

What is chronic granulomatose disease?

Answer 7

Diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the ROS

Most importantly the superoxide radical

Used to kill ingested pathogens

Question 8

What is an important process of acute inflammation?

Answer 8

Soluble mediators are synthesised at strategic checkpoints

Switch off the response and prevent chronic inflammatio, tissue injury and adaptive immune response

Question 9

Being anti-inflammatory means being pro-resolving

TRUE or FALSE

Answer 9

FALSE

Question 10

What happens to people who can’t make cortisol?

Answer 10

More exaggerated acute inflammatory responses but quicker resolution

Question 11

What are pro-inflammatory mediators?

Answer 11

Bioactive amines

Cytokines

CHemokines

Cell adhesion molecules

Question 12

What are anti-inflammatory mediators?

Answer 12

Cortisol

IL-10

TGFb

PGE2

Question 13

What are examples of historical treatments to inflammation?

Answer 13

Dried leaves of myrtle - rheumatic pains from womb

Poplar tree and willow tree - childbirth and fever

Salicyate-containing plants - water soluble from willow bark, poplar and myrtle

Question 14

What was used to synthesise aspirin?

Answer 14

Salicyate

Question 15

Who made aspirin?

Answer 15

Felix Hoffman

Question 16

How was aspirin made?

Answer 16

Salicyate tasted bad and caused stomach upset

CHemically manufactured aspirin without the side effects

Added acetyl group to salicyate

Question 17

What are the uses of aspirin?

Answer 17

Has cardiovascular protective effect and anti-inflammatory effects

Was developed without knowing the mechanism of action

Question 18

What are the problems of aspirin?

Answer 18

Concentration of apirin that reach plasma at a dose that was anti-inflammatory was much higher than expected 1

Question 19

What was a modification done to aspirin to increase its anti-inflammatory effects?

Answer 19

Bound aspirin to COX which has the products of prostaglandins

Anti-inflammatory effects

Question 20

Role of COX-derived prostaglandins

Answer 20

Pyretic

Pro-inflammatory

Hyperalgesic

Inhibit gastric acid secretion

Contract the uterus

Increase renal blood flow

Question 21

What is the future of treating inflammation?

Answer 21

Discover novel pro-resolution pathways

Tissue and disease specific

Question 22

Recent progress in treating inflammatory conditions

Answer 22

Lipid mediators and scavenging molecules found which act as waste disposal systems for pro-inflammatory cytokines

Factors that inhibit PMN trafficking

Macrophage clearance

Question 23

Important scientist in the development of understanding of phagocytes

Answer 23

Ilya Metchinkiff