Biomedical Engineering Reference
In-Depth Information
have been implicated in the pathogenesis of both septic shock and rheumatoid arthritis. Inhibiting the
biological activity of such cytokines may provide effective therapies for such conditions. This may be
achieved by administration of monoclonal antibodies raised against the target cytokine, or administra-
tion of soluble forms of its receptor that will compete with cell surface receptors for cytokine binding.
Some cytokines have already gained approval for medical use. Many more are currently under-
going clinical or preclinical trials. Over the next few chapters the biology and potential medical
applications of these cytokines will be discussed in detail. The remainder of this chapter concerns
itself with the prototypic cytokine family, namely the interferons.
8.2 The interferons
Interferons were the fi rst family of cytokines to be discovered. In 1957, researchers observed that
susceptible animal cells, if they were exposed to a colonizing virus, immediately became resistant
to attack by other viruses. This resistance was induced by a substance secreted by virally infected
cells which was named interferon. Subsequently, it has been shown that most species actually pro-
duce a whole range of interferons. Humans produce at least three distinct classes, IFN-α, IFN-β
and IFN-
(Table 8.4). These interferons are produced by a variety of different cell types and
exhibit a wide range of biological effects, including:
γ
induction of cellular resistance to viral attack;
regulation of most aspects of immune function;
regulation of growth and differentiation of many cell types;
sustenance of early phases of pregnancy in some animal species.
No one interferon will display all of these biological activities. Effects are initiated by the bind-
ing of the interferon to its specifi c cell surface receptor present in the plasma membrane of sensi-
tive cells. IFN-α and -β display signifi cant amino acid sequence homology (30 per cent), bind to
the same receptor, induce similar biological activities and are acid stable. For these reasons, IFN-
and IFN-β are sometimes collectively referred to as type I interferons, or acid-stable interferons.
α
Table 8.4 Human interferons and the cells that produce them
Interferon family
Additional name
No. distinct interferons in family
Producing cells
IFN-
α
Leukocyte interferon
15
Lymphocytes
B cell interferon
Monocytes
Lymphoblast interferon
Macrophages
IFN-β
Fibroblast interferon
1
Fibroblasts
IFN-β-1 a
Some epithelial cells
IFN-γ
Immune interferon
1
T-lymphocytes
T cell interferon
NK cells
a Originally a second cytokine was called IFN-β-2, but this was subsequently found to be actually IL-6.
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