Biomedical Engineering Reference
In-Depth Information
Some of the problems with these cytokines, including many of the IFNs and interleukins, are
their side effects, which include l u-like syndromes when given at a high dose.
22.5.3.2
Tumor Necrosis Factor
TNF-
is a proinl ammatory cytokine that is produced by macrophages, NK cells as well as B
and T cells. Its action is to promote local inl ammation, and to activate endothelial cells. TNF-
α
,
in soluble or membrane form, binds to two types of receptors that will cause the activation of the
target cell.
TNF-
α
plays a predominant part in the inl ammatory process of RA and is highly up regulated
in the synovial l uid of the joints in RA patients. TNF-
α
causes release of intra-articular metallo-
proteases, which destroy bone cartilage, and via activation of transcription factors (NF-kB), TNF-
α
α
causes the production of proinl ammatory and immunomodulating cytokines.
The implication of TNF-
in the inl ammatory process and in the destruction of bone cartilage
(RA) and in inl ammatory intestinal lesions (Crohn's disease) has enabled the development of two
approaches to treatment using TNF-
α
inhibitor agents, two mAbs and a soluble receptor, which are
used in combination with methotrexate.
There are two mAbs directed at TNF-
α
, one chimeric, Inl iximab (Remicade
®
); the other
entirely humanized, Adalimumab (Humira
®
). A soluble receptor of TNF-
α
α
, Etanercept (Enbrel
®
),
which limits the biological activity of TNF-
α
, acts by binding to it and preventing it from interact-
ing with its receptors. The TNF-
α
inhibitors are successfully used for treatment of RA, psoriasis,
and Chron's disease.
22.5.3.3 Interleukins
The role of interleukins is to mediate and control the immunologic and inl ammatory response
(Table 22.1). The list of known ILs is still increasing most of which have only been discovered in
the last few years. Their role within the immune system is only beginning to be understood and they
are just starting to be utilized in the treatment of a wide variety of diseases including cancer, AIDS,
and autoimmune diseases. The following table briel y describes the role of each of the interleukins
where the action is well understood.
TABLE 22.1
The Role of Interleukins
Interleukin
Secreting Cells
Action
IL-1
Macrophages
Stimulates T cells to secrete interleukin-2 and activate the
inl ammatory response. It also causes the hypothalamus to increase
the body temperature.
IL-2
Helper T cells
Causes activated T- and B cells to proliferate themselves. It also
induces antibody synthesis.
IL-3
T cells
Causes other leukocytes to be proliferated—it does this by making
certain types of stem cell in the bone marrow to differentiate and
grow.
IL-4
Helper T cells
Causes T- and B cells to grow. It is also a factor in the production of
IgE antibodies.
IL-5
Helper T cells
Stimulates B cells, and eosinophils. It causes B cells that produce
IgA antibodies to proliferate
IL-6
T cells and macrophages
Works in combination with alpha interferon to induce B cell
differentiation. It also causes the production of acute phase proteins
in the liver and stimulates T cells and other leukocytes.
IL-7
Stromal cells
Causes lymphoid stem cells to differentiate into progenitor T and B
cells.
