Targeting TNF And IL1 Signalling In Chronic Inflammation Flashcards
Explain why the current anti-inflammatory drugs (COX2 and histamine inhibitors) aren’t ideal for treating inflammation long term (in chronic conditions)
They can’t distinguish between sterile and infectious inflammation - and therefore diminish people’s ability to fight infections
What is the major role that TNF plays in chronic inflammation?
Major chemoattractant that recalls lymphocytes to the site of inflammation
Promotes fibroblast migration and proliferation (therefore favours fibrosis)
Why is TNF a good therapeutic target?
It perpetuates inflammation even without the presence of an infectious agent
What are the 2 groups of caspases in humans
Apoptotic caspases and Inflammatory caspases
Name the inflammatory caspases
Caspase 1, 4 and 5
What is the role of Caspase 1?
To convert pro-IL1 into active IL1
DAMP binds to receptor in the presence of IL1… What happens next?
The inflammasome is assembles, caspase 1 is activated and it goes on to active pro-IL1 to active IL1
Why is it that by inhibiting IL1 we can inhibit sterile inflammation in a major way, but not infectious inflammation?
This is because there is far more redundency in infectious inflammation than in sterile inflammation.
Why would IL1 inhibitors be preferable to COX2 inhibitors?
They would only target sterile inflammation
What are the 3 genes for IL1? What do they encode?
IL1 alpha - a receptor agonist
IL1 beta - the most potent receptor agonist
IL1 RA - a receptor antagonist
Describe the focuses of current studies to inhibit IL1
- Creating a recombinant form of IL1 RA in order to block the action of IL1 via competitive inhibition
- Creating antibodies AGAINST IL1 beta
