Tumor necrosis factor-alpha (TNF-A)

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SYNONYMS

Lymphotoxin B, Cachectin.

http://www.bio.davidson.edu/courses/immunology/Students/spring2000/wo

lf/tnfalpha.html

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FUNCTION

Tumor necrosis factor-alpha (TNF-A) is a pleiotropic inflammatory

cytokine. It was first isolated by Carswell et al. in 1975 in an

attempt to identify tumor necrosis factors responsible for necrosis

of the sarcoma Meth A (Carswell et al., 1975). Most organs of the

body appear to be affected by TNF-A, and the cytokine serves a

variety of functions, many of which are not yet fully understood.

The cytokine possesses both growth stimulating properties and growth

inhibitory processes, and it appears to have self regulatory

properties as well. For instance, TNF-A induces neutrophil

proliferation during inflammation, but it also induces neutrophil

apoptosis upon binding to the TNF-R55 receptor (Murray, et al.,

1997). The cytokine is produced by several types of cells, but

especially by macrophage. Tracey and Cerami suggest two beneficial

functions of TNF-A which have lead to its continued expression

(1990). First, the low levels of the cytokine may aid in

maintaining homeostasis by regulating the body's circadian rhythm.

Furthermore, low levels of TNF-A promote the remodeling or

replacement of injured and senescent tissue by stimulating

fibroblast growth.

Additional beneficial functions of TNF-A include its role in the

immune response to bacterial, and certain fungal, viral, and

parasitic invasions as well as its role in the necrosis of specific

tumors. Lastly it acts as a key mediary in the local inflammatory

immune response. TNF-A is an acute phase protein which initiates a

cascade of cytokines and increases vascular permeability, thereby

recruiting macrophage and neutrophils to a site of infection. TNF-A

secreted by the macrophage causes blood clotting which serves to

contain the infection. Without TNF-A, mice infected with gram

negative bacteria experience septic shock (Janeway et al., 1999).

The pathological activities of TNF-A have attracted much attention.

For instance, although