Biomedical Engineering Reference
In-Depth Information
The cytokines: The interferon family
8.1 Cytokines
Cytokines are a diverse group of regulatory proteins or glycoproteins whose classifi cation remains
somewhat diffuse (Table 8.1). These molecules are normally produced in minute quantities by the
body. They act as chemical communicators between various cells, inducing their effect by bind-
ing to specifi c cell surface receptors, thereby triggering various intracellular signal transduction
events. Over the next several chapters we consider various cytokines of therapeutic interest, focus-
ing in particular upon those approved for clinical application.
Most cytokines act upon, or are produced by, leukocytes (white blood cells), which constitute
the immune and infl ammatory systems (Box 8.1). They thus play a central role in regulating both
immune and infl ammatory function and in related processes such as haematopoiesis (the produc-
tion of blood cells from haematopoietic stem cells in the adult bone marrow), as well as in wound
healing. Indeed, several immunosuppressive and anti-infl ammatory drugs are now known to in-
duce their biological effects by regulating production of several cytokines.
The term 'cytokine' was fi rst introduced in the mid 1970s. It was applied to polypeptide growth fac-
tors controlling the differentiation and regulation of cells of the immune system. The interferons and
interleukins represented the major polypeptide families classifi ed as cytokines at that time. Additional
classifi cation terms were also introduced, including lymphokines (cytokines such as IL-2 and IFN-γ,
produced by lymphocytes) and monokines (cytokines such as TNF-
, produced by monocytes). How-
ever, classifi cation on the basis of producing cell types also proved inappropriate, as most cytokines
are produced by a range of cell types (e.g. both lymphocytes and monocytes produce IFN-
α
).
Initial classifi cation of some cytokines was also undertaken on the basis of the specifi c biologi-
cal activity by which the cytokine was fi rst discovered (e.g. TNF exhibited cytotoxic effects on
some cancer cell lines; CSFs promoted the growth
in vitro
of various leukocytes in clumps or colo-
nies). This, too, proved an unsatisfactory classifi cation mechanism, as it was subsequently shown
that most cytokines display a range of biological activities (e.g. the major biological function of
TNF is believed to be as a regulator of both the immune and infl ammatory response). More re-
cently, primary sequence analysis of cytokines coupled to determination of secondary and tertiary
structure reveal that most cytokines can be grouped into one of six families (Table 8.2).
α
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