Chronic inflammation II

Question 1

What is most of the driving of chronic inflammation caused by?

Answer 1

Cytokines

Question 2

Which cells produce cytokines?

Answer 2

Leukocytes

Question 3

Effect of activation of immune cells on cytokines?

Answer 3

Upregulate cytokine receptors, produce more cytokines

Question 4

Pro-inflammatory cytokines?

Answer 4

IL1, TNF, Interferon gamma, IL8, IL6

Question 5

Anti-inflammatory cytokines?

Answer 5

IL4, IL5, IL10, IL13, IL1-RA

Question 6

Which cytokines are B cell activators?

Answer 6

IL4, IL5

Question 7

Which cytokines are raised in asthma?

Answer 7

IL4, IL13, IL5

Question 8

What should the secretion of cytokines be?

Answer 8

Brief and self limiting

Question 9

When are cytokines made?

Answer 9

Synthesised as required or activated by proteolytic cleavage

Question 10

Cytokine system being promiscuous and redundant?

Answer 10

One cytokine acts on many cell types
One cell type can produce many different cytokines

Question 11

Issue with anti-inflammatory therapies?

Answer 11

Inflammation is still needed to fight other infections, so cant just dampen it all down

Question 12

Primary cytokines for chronic inflammation?

Answer 12

IL1, TNFalpha

Question 13

WHat can IL1 and TNFa drive?

Answer 13

Cell proliferation, TNF can also cause apoptosis

Question 14

How can TNFa cause cell proliferation and apoptosis?

Answer 14

Its effect depends on which intracellular signalling molecules it recruits to the receptor, and which pathway it activates

Question 15

What is NFkappab?

Answer 15

Pro inflammatory TF–> leads to self proliferation

Question 16

WHich cells produce both IL1 and TNFa?

Answer 16

LPS-activated monocytes/macrophages

Question 17

What effect do IL1 and TNFa have on each other?

Answer 17

Upregulate each other

Question 18

Which form of IL1 is membrane bound and intracellular?

Answer 18

IL1alpha

Question 19

Which form of IL1 is circulating and soluble?

Answer 19

IL1beta

Question 20

What happens of IL1 is put into animals, then blocked?

Answer 20

Initially causes inflammation and fever, then after blocking the disease is reduced

Question 21

Effect of IL1 on bones?

Answer 21

Bone erosion
Activates osteoclasts through activating RANKligand cytokine

Question 22

What does Cox-2 lead to?

Answer 22

Inflammatory prostaglandins

Question 23

How is IL1 synthesised?

Answer 23

As a precursor

Question 24

What cleaves the IL1 precursor?

Answer 24

Interleukin-1 converting enzyme (ICE)
aka caspase 1

Question 25

ICE inhibitors potential?

Answer 25

Anti-inflammatory agents--> would not cleave IL1b and so keep it in the host cell

Question 26

What facilitates the release of IL1b?

Answer 26

ATP binding to receptor P2X7

Question 27

Possibility of P2X7 antagonists

Answer 27

Anti-inflammatory

Question 28

Gene therapy approach to inflammatory diseases?

Answer 28

Put in lots of genes for anti-inflammatory cytokines Tried to use tissue specific promoters--> joints only

Question 29

Potential genes targeted by gene therapy?

Answer 29

NFkappab inhibitors, FADD (fas actiated death domains)

Question 30

Role of FADD?

Answer 30

Induction of apoptosis

Question 31

What is anakinra?

Answer 31

IL1 receptor antagonist

Question 32

Effect of anakinra?

Answer 32

Effective in the joint it was injected in, and other joints--> issue

Question 33

Forms of IL1?

Answer 33

Membrane bound and soluble

Question 34

How does TNFa bind?

Answer 34

As a trimer