Biomedical Engineering Reference
In-Depth Information
Figure 8.1
Cytokine receptors usually display a unique cytokine ('ligand')-binding domain, but they share
additional receptor components that are normally responsible for signal transduction. This explains the
molecular basis of pleiotropy. IL-6, IL-11 and LIF receptors, for example, are all composed of a distinct
ligand-specifi c binding domain and a separate subunit (gp 130). gp 130 is responsible for initiating signal
transduction and is identical in all three receptors. This is depicted schematically above
Some cytokine receptors can directly initiate signal transduction upon binding of ligand. In
other cases additional elements are involved. For many receptors, the exact intracellular events
triggered upon ligand binding remain to be elucidated. However, the molecular details of signal
transduction pathways for others (e.g. the interferons) are now understood
8.1.2 Cytokines as biopharmaceuticals
Cytokines, in many ways, constitute the single most important group of biopharmaceutical sub-
stances. As coordinators of the immune and infl ammatory response, manipulation of cytokine
activity can have a major infl uence on the body's response to a variety of medical conditions. Admin-
istration of certain cytokines can enhance the immune response against a wide range of infectious
agents and cancer cells. EPO has proven effective in stimulating red blood cell production in anae-
mic persons. Growth factors have obvious potential in promoting wound healing. And neurotrophic
factors display some clinical promise in the abatement of certain neurodegenerative diseases.
A better understanding of the molecular principles underlining cytokine biology may also pro-
vide new knowledge-based strategies aimed at defeating certain viral pathogens. These pathogens
appear to establish an infection successfully, at least in part, by producing specifi c proteins that
thwart the normal cytokine-based immunological response. The cowpox virus, for example, pro-
duces an IL-1-binding protein, and the shope fi broma virus produces a TNF-binding protein. The
Epstein-Barr virus, on the other hand, produces a protein homologous to IL-10.
A variety of medical conditions are now believed to be caused or exasperated by overproduction of
certain cytokines in the body. A variety of pro-infl ammatory cytokines, including IL-6, -8 and TNF,
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