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6

Messenger Targets for Drug Action III

Immunomodulators and their receptors

The final messenger system that can be exploited for purposes of understanding drug
action is the immune system. The function of the immune system is to preserve the
integrity of the body at a cellular level. It is designed to eliminate pathogens and to pro-
tect the host. In fulfilling this goal, the immune system makes extensive use of white
blood cells as cellular messengers and mediators. Like neural and endocrine messenger
systems, the immune system is capable of manipulating biochemical information for
the purpose of maintaining homeostasis and combating disease. The immune system
stores information concerning previous infections and transmits information through
the integrated use of cellular (white blood cell) and molecular (cytokine) elements.
The immune system is well integrated with the two other principal messenger systems.
For example, steroid molecules exert a significant effect upon both the immune and
endocrine systems, representing a molecular overlap between the hormonal and immune
messenger networks. Various researchers are also investigating a possible interaction
between the nervous system and the immune system; for instance, can a neurochemically
mediated psychiatric disorder, such as severe depression, lead to a suppression of immune
system functioning? Although somewhat controversial, this remains a fascinating area of
research, rich in potential. Such opportunities must be explored, since the immune system
possesses numerous valuable druggable targets for drug design.
The immune system also represents an important messenger system for drug design
as applied to chronic inflammatory diseases, including rheumatoid arthritis, bronchial
asthma, and inflammatory bowel disease. As discussed in this chapter, cytokines and
their receptors are the key druggable target molecules within the immune system; in
future, they will undoubtedly emerge as important drug design targets for the treatment
of chronic inflammatory diseases such as rheumatoid arthritis.

6.1 Overview of the Immune System as a Source of Drug Targets

The immune system responds when the normal, healthy operation of the body (home-
ostasis) is perturbed. In response to such a perturbation, the immune system orchestrates