Resolution to inflammation Flashcards
What are the steps of inflammation
Bee sting/ infection
Local release of inflammatory hormones
White blood cells from circulation transmigrate towards site of infection
Monocytes differentiate into macrophages
Acute inflammation
What are treatments of acute inflammation?
Steroids
Anti-TNFa
NSAIDS
What is resolution?
Active process
State caused by the removal of the inducible factors
Cause of inflammation are removed
What are the requirements for reslution?
Clearance of stimulus
Chemokine catabolism
Decreased leukocyte trafficking
Apoptosis/ phagocytosis
Pro-resolution macrophages
WHat happens if resolution does not happen correctly?
Break immune tolerance
Set the scene for autoimmunity and chronic inflammation
What happens in failed resolution?
Bacteria not cleared
Grow and multiply
WBCs enter tissue
Stromal cells are angry and make more collagenous ECM = more granulomatose tissue
Chronic inflammation
What is chronic granulomatose disease?
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
What is an important process of acute inflammation?
Soluble mediators are synthesised at strategic checkpoints
Switch off the response and prevent chronic inflammatio, tissue injury and adaptive immune response
Being anti-inflammatory means being pro-resolving
TRUE or FALSE
FALSE
What happens to people who can’t make cortisol?
More exaggerated acute inflammatory responses but quicker resolution
What are pro-inflammatory mediators?
Bioactive amines
Cytokines
CHemokines
Cell adhesion molecules
What are anti-inflammatory mediators?
Cortisol
IL-10
TGFb
PGE2
What are examples of historical treatments to inflammation?
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
What was used to synthesise aspirin?
Salicyate
Who made aspirin?
Felix Hoffman
How was aspirin made?
Salicyate tasted bad and caused stomach upset
CHemically manufactured aspirin without the side effects
Added acetyl group to salicyate
What are the uses of aspirin?
Has cardiovascular protective effect and anti-inflammatory effects
Was developed without knowing the mechanism of action
What are the problems of aspirin?
Concentration of apirin that reach plasma at a dose that was anti-inflammatory was much higher than expected 1
What was a modification done to aspirin to increase its anti-inflammatory effects?
Bound aspirin to COX which has the products of prostaglandins
Anti-inflammatory effects
Role of COX-derived prostaglandins
Pyretic
Pro-inflammatory
Hyperalgesic
Inhibit gastric acid secretion
Contract the uterus
Increase renal blood flow
What is the future of treating inflammation?
Discover novel pro-resolution pathways
Tissue and disease specific
Recent progress in treating inflammatory conditions
Lipid mediators and scavenging molecules found which act as waste disposal systems for pro-inflammatory cytokines
Factors that inhibit PMN trafficking
Macrophage clearance
Important scientist in the development of understanding of phagocytes
Ilya Metchinkiff
