Biomedical Engineering Reference
In-Depth Information
•
induction/regulation of infl ammation;
•
selective cytotoxic activity against a range of tumour cells;
•
mediation of various pathological conditions, including septic shock, cachexia and anorexia.
is dependent upon a number of factors,
most notably the level at which TNF-α is produced. At low concentrations, TNF-α acts locally in
a paracrine and autocrine manner, predominantly infl uencing white blood cells and endothelial
cells. Under such circumstances, TNF-α's major activity relates to regulation of immunity and
infl ammation. In some situations, however, very large quantities of TNF-
The exact range of biological effects induced by TNF-
α
may be produced
(e.g. during severe Gram-negative bacterial infections). In such instances, TNF-α enters the blood
stream and acts in an endocrine manner. Systemic effects of TNF-
α
(systemic means relating to the
whole body, not just a specifi c area or organ), which include severe shock, are largely detrimental.
Prolonged elevated systemic levels of TNF-
α
induce additional effects on, for example, whole-body
metabolism. Many of TNF-α's biological effects are augmented by interferon-γ.
α
9.5.3 Immunity and infl ammation
At low concentrations, TNF-α activates a range of leukocytes that mediate selected elements of
both specifi c and non-specifi c immunity. These TNF-
α
actions include:
•
activation of various phagocytic cells, including macrophages, neutrophils and polymorphonu-
clear leukocytes;
•
enhanced toxicity of eosinophils and macrophages towards pathogens;
•
exerting antiviral activity somewhat similar to class I interferons, and increasing surface
expression of class I MHC molecules on sensitive cells;
•
enhancing proliferation of IL-2-dependent T-lymphocytes.
infl uences immunity indirectly by promoting synthesis and release of a
variety of additional cytokines, including interferons, IL-1, IL-6, IL-8 and some CSFs.
TNF-
In addition, TNF-
α
also plays a prominent role in mediating the infl ammatory response; indeed, this may be
its major normal physiological role. It promotes infl ammation by a number of means, including:
α
•
Promoting activation of neutrophils, eosinophils and other infl ammatory leukocytes.
•
Induction of expression of various adhesion molecules on the surface of vascular endothelial
cells. These act as docking sites for neutrophils, monocytes and lymphocytes, facilitating their
accumulation at local sites of infl ammation.
•
Displays chemotactic effects, especially for monocytes and polymorphonuclear leukocytes.
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