Biomedical Engineering Reference
In-Depth Information
Cytokines: Interleukins and tumour
necrosis factor
9.1 Introduction
The interleukins represent another large family of cytokines, with at least 33 different constituent
members (IL-1 to IL-33) having been characterized thus far. Most of these polypeptide regu-
latory factors are glycosylated (a notable exception being IL-1) and display a molecular mass
ranging from 15 to 30 kDa. A few interleukins display a higher molecular mass, e.g. the heavily
glycosylated, 40 kDa, IL-9.
Most of the interleukins are produced by a number of different cell types. At least 17 different
cell types are capable of producing IL-1, and IL-8 is produced by at least 10 distinct cell types. On
the other hand, IL-2, -9 and -13 are produced only by T-lymphocytes.
Most cells capable of synthesizing one interleukin are capable of synthesizing several, and
many prominent producers of interleukins are non-immune system cells (Table 9.1). Regu-
lation of interleukin synthesis is exceedingly complex and only partially understood. In most
instances, induction or repression of any one interleukin is prompted by numerous regulators
(mostly additional cytokines). IL-1, for example, promotes increased synthesis and release of IL-2
from activated T-lymphocytes. It is highly unlikely that cells capable of synthesizing multiple
interleukins concurrently synthesize them all at high levels.
Nearly all of the interleukins are soluble molecules (one form of IL-1 is cell associated). They
promote their biological response by binding to specifi c receptors on the surface of target cells.
Most interleukins exhibit paracrine activity (i.e. the target cells are in the immediate vicinity of the
producer cells), although some display autocrine activity (e.g. IL-2 can stimulate the growth and
differentiation of the cells that produce it). Other interleukins display more systematic endocrine
effects (e.g. some activities of IL-1).
T h e s ig n a l t r a n s d u c t io n m e c h a n i s m s by wh ic h m o s t i n t e r l e u k i n s p r o m p t t h e i r b iolog ic a l r e s p o n s e
are understood, in outline at least. In many cases, interleukin cell surface receptor binding is
associated with intracellular tyrosine phosphorylation events. In other cases, serine and threo-
nine residues of specifi c intracellular substrates are also phosphorylated. For some interleukins,
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