In the previous tutorial we discussed a number of immunomodulators that have an immunosuppressive
effect. We will now move on to immunostimulatory drugs. These drugs are often used to treat
conditions that suppress the immune system, but also just as commonly as a corrector to balance
unintentional immune system suppression, for example from some anti-cancer chemotherapy drug
treatment. The other use these drugs have is in the treatment of some immune system related
cancers. Since the immune system can recognize some tumor cells and target them for apoptosis,
some immune stimulating drugs have anti-cancer properties.
There are four main classes of immunostimulatory drugs. These are colony stimulating factors,
interleukins, interferons, and vaccines. In this tutorial we won’t discuss vaccines,
as these have been discussed in more than one context in my tutorials on immunology,
the history of drugs, as well as debunking content. So let’s focus on the other three.
Colony stimulating factors act to enhance the production, maturation, and bone marrow release of
various types of white blood cells into the blood. These factors are often present endogenously, but
recombinant forms are sometimes given exogenously. By enhancing the overall count of white blood
cells it’s easy to see how this general mechanism leads to immune system stimulation.
Specific drugs in this class usually mediate their immunostimulatory effect
by influencing the enhancement of a specific type of white blood cell. To give a brief example,
filgrastim is a recombinant human methionyl granulocyte colony-stimulating factor.
It acts to enhance functionality of neutrophil progenitors via enhancement of production,
maturation, and release into the blood. This class of immunostimulant is used to treat neutropenia,
a condition characterised by a low concentration of neutrophils. This is often caused by a range
of circumstances, for example in patients receiving myelosuppressive chemotherapy,
people suffering from AIDS, chronic B12 deficiency, as well as many other situations.
Next, exogenous interleukins are sometimes used pharmacologically such as oprelvekin and
aldesleukin. These drugs are recombinant IL-11 and IL-2 respectively. As we touched on earlier
when discussing immunophilin binding drugs, interleukins are immune-stimulating chemokines.
However, it is worth bearing in mind that recombinant interleukins,
although sometimes helpful in some immunocompromised conditions, are mainly
used in the clinic for some types of cancer, where immune function has been impaired either directly
by the cancer, such as multiple myeloma, or indirectly via anti-cancer chemotherapy drugs.
Finally, we can briefly discuss interferons. Interferons, like interleukins, are a large
family of endogenous chemokines that are sometimes given exogenously for some viral infections,
as well as some cancers, to enhance the immune response against viruses and tumor cells. The
primary mechanism interferons elicit is through the interferon receptor located on the plasma
membrane of most white blood cells. Following a complex intracellular signaling cascade,
interferon regulatory factors are activated. These are transcription factors that increase
the protein production of various immune stimulating proteins such as cytokines,
and proteins essential for the development and maturation of natural killer cells, B and T cells.
In closing, it’s important to appreciate the wide range of immunomodulatory drugs.
The goal of this series is not necessarily to be totally exhaustive, but to cover commonly used
drugs and important pharmacological mechanisms in such a way that, should you encounter other drugs
in a particular class, you can apply the thematic understanding you gain from these tutorials
to efficiently comprehend mechanisms of other similar acting drugs and how they achieve their
pharmacological effect. And with that, we can now move on to an entirely different class of drugs.