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Tumor Necrosis Factor

The Good, the Bad, and the Umbra
  • Steven W. Barger
Chapter
Part of the Contemporary Neuroscience book series (CNEURO)

Abstract

The pace at which connections are being drawn between the nervous system and the immune system does not appear to be slowing. Although the relationship between these two systems is more commonly discussed in terms of concrete interactions modulating physiology, it can be expanded to include more abstract considerations, such as analogies between molecules and between basic principles of operation. Thus, we have come to see beyond the responsiveness of leukocytes to neuropeptides and neuromodulators like CRH and morphine, to recognize relationships exemplified by the compatibility between the principles of antigen presentation and Hebbian arguments about associative synaptic plasticity. Similarly, one can argue that innoculation is a form of conditioning and that neurons may be conditioned not only to strengthen a circuit required for information storage, but that they may also be conditioned to withstand greater metabolic demands or injurious conditions. The central nervous system (CNS) certainly maintains a degree of immune privilege; therefore, one must consider the role of resident leukocytes (i.e., microglia). That they help to combat infections is obvious, but microglia also respond to noninfectious pathologies with reactions more complex than the staid phagocytosis of debris; it is difficult to imagine that retention of the latter responses by evolution is accidental. This chapter focuses on a specific component of gliotic mediators, tumor necrosis factor (TNF). Some of the data discussed distinguishes between TNFα (cachectin) and TNFβ (lymphotoxin-α). However, their mechanisms of action and the responses of relevant target cells are similar enough that the more inclusive TNFs or TNF- will be used often to describe these shared actions. Emphasis is given to the role of TNFs in brain injury responses and to data that force consideration of the possibility that TNF expression in the CNS may have beneficial influences, particularly with respect to conditioning that enhances neuronal resistance to insults.

Keywords

Tumor Necrosis Factor Tumor Necrosis Factor Receptor Death Domain Kainic Acid SMase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer Science+Business Media New York 1998

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  • Steven W. Barger

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