Biomedical Engineering Reference
In-Depth Information
Most cytokines are produced by a variety of cell types, which may be leukocytes or non-leukocytes,
e.g. IL-1 is produced by a wide range of cells, including leukocytes (such as monocytes, macro-
phages, NK cells, B- and T-lymphocytes) and non-leukocytes (such as smooth muscle cells, vascular
endothelial cells (a single layer of cells lining blood vessels), fi broblasts (cells found in connective tis-
sue that produce ground substance and collagen fi bre precursors), astrocytes (non-neural cells found
in the central nervous system) and chondrocytes (cells embedded in the matrix of cartilage)).
Many cell types can produce more than one cytokine. Lymphocytes, for example, produce a
wide range of interleukins, CSFs, TNF, IFN-
α
s and IFN-
γ
. Fibroblasts can produce IL-1, -6, -8,
and -11, CSFs, IFN-β and TNF.
Many cytokines play a regulatory role in processes other that immunity and infl ammation.
Neurotrophic factors, such as NGF and BDNF, regulate growth, development and maintenance
of various neural populations in the central and peripheral nervous system. EPO stimulates the
production of red blood cells from erythroid precursors in the bone marrow.
Most cytokines are pleiotropic, i.e. can affect a variety of cell types. Moreover, the effect that
a cytokine has on one cell type may be the same or different to its effect on a different cell
type. IL-1, for example, can induce fever, hypotension and an acute phase response. G-CSF is
a growth factor for neutrophils, but it is also involved in stimulating migration of endothelial
cells and growth of haematopoietic cells. IFN-
stimulates activation and growth of T- and B-
lymphocytes, macrophages, NK cells, fi broblasts and endothelial cells. It also displays weak
anti-proliferative activity with some cell types.
γ
Most cytokines are inducible, and are secreted by their producer cell, e.g. induction of IL-2 synthe-
sis and release by T-lymphocytes is promoted by binding of IL-1 to its receptor on the surface of
T cells. IFN-
s are induced by viral intrusion into the body. In general, potent cytokine inducers
include infectious agents, tissue injury and toxic stimuli. The bodies main defence against such
agents, of course, lies with the immune system and infl ammation. Upon binding to target cells, cy-
tokines can often induce the target cell to synthesize and release a variety of additional cytokines.
α
In contrast, some cytokines (e.g. some CSFs and EPO) appear to be expressed constitutively. In yet
other instances cytokines such as PDGF and TGF-
are stored in cytoplasmic granules and can be
rapidly released in response to appropriate stimuli. Other cytokines (mainly ones with growth fac-
tor activity, e.g. TGF-
β
, FGF and IL-1) are found bound to the extracellular matrix in connective
tissue, bone and skin. These are released, bringing about a biological response upon tissue injury.
β
Many cytokines exhibit redundancy, i.e. two or more cytokines can induce a similar biological
effect. Examples include TNF-
, both of which bind to the same receptor and induce
very similar, if not identical, biological responses. This is also true of the IFN-α family proteins
and IFN-
α
and -
β
β
, all of which bind the same receptor.
Although all cytokines are polypeptide regulatory factors, not all polypeptide regulatory factors
are classifi ed as cytokines. Classical polypeptide hormones, such as insulin, FSH and GH are not con-
sidered members of the cytokine family. The distinguishing features between these two groups is ill
defi ned, and in many ways artifi cial. Originally, one obvious distinguishing feature was that hormones
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