40.3 Iatrogenic and Therapeutic Immunosuppression

Question 1

What treatments can cause iatrogenic immunosuppression?

Answer 1

It can be a complication of cytotoxic drug use or irradiation in tumour therapy. Can lead to neutropenic sepsis.

Question 2

Why is immunosuppression a side effect of cytotoxic drug use?

Answer 2

These therapies tend to target rapidly dividing populations of cells including haematopoietic stem cells and their myeloid/ lymphoid derivatives –> depleted immunity.

Question 3

What is Neutropenic sepsis?

Answer 3

high bacteraemia is seen in the presence of a reduced neutrophil count as a result of myelosuppressive therapies or other defects (eg. chronic granulomatous disease, Chediak-Higashi syndrome, etc.)

Question 4

Why would we want therapeutic immunosuppression?

Answer 4

After transplantation surgery or to control auto-immune disease.

Question 5

How can therapeutic immunosuppression be achieved?

Answer 5

*NSAIDS - COX inhibitors that reduce leukocyte recruitment and activation so that the immune response is harder to initiate.
*Glucocorticoids - high doses are able to upregulate anti-inflammatory cytokine production and interfere with NF-κB expression to decrease it.
More specific:
*Calcineurin - inhibit T-cell activation
*Biologicals (e.g. anti-TNF) - target specific signalling molecules