Cytokines

Question 1

What is the role of Cytokines in Inflammation response? And how does this work?

Answer 1

Conduct the inflammatory signal to Immune cells (communication between them).
Extracellular cytokines interacts with receptor on the Immune cell surface –> intercellular signal cascade –> cell response
Often synergistic effect of cytokines

Question 2

What does
Pleiotropy
Redundancy
Synergy and
Antagonism refers to?

Answer 2

Pleiotropy - one cytokine has dofferent effects on different cells
Redundancy - Same effect by different cytokines
Synergy - Stronger effect by multiple Cytokines
Antagonism - competing inverese effect of different cytokines

Question 3

Which of the following Cytokines are pro- and which are antiinflamatory ?
Il-1, Il-4, Il-6, IL-10, IL-12, IL-13, TNFalpha, TNFbetta

Answer 3

Pro: IL1,IL6,IL12,TNFalpha
Con: IL10,IL4,IL13,TNFbetta

Question 4

What is the difference between IL1alpha and IL1betta ?

Answer 4

both are pro inflamatory Cytokines and have a similar effect.
IL1a - acts locally and is produced by endothelial cells
IL1b - acts systematically produced by macrophages and monocytes

Question 5

IL18

Answer 5

Continually expressed by monocytes, DC and Endothelial cells only activated when Caspase1 is active (when cell is stressed, pathogens are present or the cell is apoptotic)

Question 6

IL33

Answer 6

Pro and anti inflammatory, is produced by endothelial and epithelial cells, activates and recruits Thelper cells.

Question 7

Name a disease that is associated with the IL1 family (IL1a,ILb,IL18,IL33)

Answer 7

Asthma, Systematic Lupus, Chron’s disease.

Question 8

IL6

Answer 8

Pro inflamatory, produced by Phagocytes, TC,..
- Maturation of BC
- TC activation, differentiation and regulation
Disease: Rheumatoid arthritis (blocking of IL6 helps with symptoms), Tumors, inflamatory diseases

Question 9

TNFalpha

Answer 9

Pro inflamatory.
- Cell prolifereation of Immune cells, anti viral and anti immunoregulative
Disease: Rheumatoid arthritis –> Humira = humaized mAb against TNFa

Question 10

Il2

Answer 10

• Growth of Thelper, Treg (CD4) and cytotoxic TC (CD8) –> pro and anti inflamatory
• Formation of memory TC form CD8+ TC
  Disease: Used against melanomas as systematic injection –> mayor problem CRS

Question 11

CRS

Answer 11

= Massive TC stimmulation
Activation of TC by cytokines, which themselve produce more pro inflamatory cytokines, that activate more TC,…..
Leads to systematic inflamation, potentially life threatening.

Question 12

What are challenges concerning Cytokine therapeutics?

Answer 12

• Small t_0.5
• Systematic administration leads to limmeted efficacy and CRS
  –> therefore only given in late stage disease, when the immune system is already depleted and needs to be re activated.