Where there is a will, there is a way. Where there is no way we will find one and
build one.
Cytokines: the Past or the Future?
 Conclusion

As research advances and tools are improved to understand the immune system, more
is being learned about cytokines. There is increased interest in harnessing the language
of the immune system to direct its responses and improve health. This research holds
great potential, though the road to realizing it will likely be riddled with failed
experiments and confounding results. Cytokine therapy is not merely a tool of the
future -- years from the grasp of our medicine cabinets.
Words differently arranged have a different meaning, and meanings differently
arranged have a different effect.

Blaise Pascal (1623–1662)

Science is wonderfully equipped to answer the question ‘How?’ but it gets terribly
confused when you ask the question ‘Why?’.

Erwin Chargraff
Our knowledge is a little island in a great ocean of non-knowledge.

Isaac Bashevis Singer

We don’t know who we are until we see what we can do

Martha Grimes
CLINICAL APPLICATION OF CYTOKINES
AND CYTOKINE INHIBITION
Cytokines approved for use in cancer
Assays for cytokines
Types of cytokines
Cytokines may be divided into six groups: interleukins, colony-stimulating factors,
interferons, tumor necrosis factor, growth factors, and chemokines.
 Clinical Use of Cytokines
• Interferons a (“Roferon”, “Alferon-N”, “Intron A”) – antiviral
therapy (chronic Hepatatis B and C), hairy cell leukemia.
• Interferon b (“Betaseron”) – multiple sclerosis.
• G-CSF (“Neupogen”)– supportive treatment for bone
marrow transplantation.
• Interferon g (“Actimunne”) – chronic granulomatosis.
• Epo (“Procrite”)– kidney disorders.
• GM-CSF, IFN-g, IL2, TNF – all toxic when applied
systemically.
Cytokines maybe characterized aspleiotropic ,redundant ormultifunctional.
•Pleiotropic cytokines can act on a number of different types of cells rather than a
single cell type.
•Redundant defines the ability of a number of different cytokines to carry out the
same function.
•Multifunctional cytokines are able to regulate a number of different functions.

Cytokines are often produced in a cascade, as one cytokine stimulates its target cells
to make additional cytokines. Cytokines can act synergistically or antagonistically.
There are three functional categories of cytokines depending on whether they
(a)Regulate innate immune responses
(b) Influence adaptive immune responses
(c) Stimulate haematopoiesis
Cytokine-related diseases

Bacterial septic shock

endotoxins (cell walls) stimulate production
of IL-1 and TNF-

Cancers of lymphoid system- overproduction

of cytokines such as IL-6 (B-cell) or IL-5
(Hodgkin’s disease) or IL-2 (adult T-cell
leukemia)

Chagas’ disease (parasitic)- suppression of

-subunit of IL-2 receptor
Cytokine therapies

Interferons
IFN-- certain types of tumors
IFN-- multiple sclerosis
these are antiviral
IFN-- chronic granulomatous disease

IL-2- certain types of cancer

infusion
LAK (lymphokine-activated killer) cells
TILs (tumor-infiltrating lymphocytes)

GM-CSF- immune deficiencies

TNF (tumor necrosis factors)
TNF- and 

In some cases inhibit proliferation of tumor

cells but not normal cells

May damage vascular endothelial cells in

tumors, thus inhibiting blood supply
to the tumor
 Strategies to modulate the immune response

e.g., to reduce graft rejection (p. 293)

Toxin-conjugated cytokines: kill TH cells
and prevent graft rejection

Problems:
rapidly cleared from system
can be very toxic
doses are hard to control

Possible solutions:
ex vivo cell culture
conjugate cytokines to other molecules
modify cytokines?
 Cytokine-Related Diseases

• Bacterial septic shock

– Cytokine overproduction
– Bacterial cell-wall endotoxinsmarcophage to overproduce IL-1
and TNF-
• Bacterial toxic shock and similar deases
– Bacteria produce toxins that act as superantigens
– The large number of T cells activated o result in excessive
production of cytokines
• Lymphoid and myeloid cancers
– Cytokines and their receptors abnormally producted
– IL-6 overproduction plasmacytosis cancer
Therapeutic Use of Cytokines and
Their Receptors