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The acute and sensitization effects of tumor necrosis factor-α: implications for immunotherapy as well as psychiatric and neurological conditions

Published online by Cambridge University Press:  24 June 2014

Shawn Hayley ,
Zul Merali  and
Hymie Anisman
Shawn Hayley*
Affiliation:
Institute of Neuroscience, Carleton University, Ottawa
Zul Merali
Affiliation:
Institute of Mental Health Research, Royal Ottawa Hospital, Ottawa, Ontario, Canada
Hymie Anisman
Affiliation:
Institute of Neuroscience, Carleton University, Ottawa Institute of Mental Health Research, Royal Ottawa Hospital, Ottawa, Ontario, Canada
*
Shawn Hayley, Life Science Research Building, Carleton University, Ottawa, Ontario K1S 5B6 Canada. Tel: + (613) 520–2699; Fax: + (613) 520–4052; E-mail: [email protected]
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Abstract

In addition to their role as signaling molecules of the immune system, cytokines may participate in central neurotransmission. Variations of the central and/or peripheral levels of the proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-β (IL-1β), impact on neuroendocrine processes as well as central neurotransmitter activity. To a considerable extent, these effects are reminiscent of those elicited by psychogenic stressors. The current review describes recent findings consistent with a role for these cytokines in the neurochemical and behavioral manifestations of clinical depression, as well as the cellular death associated with cerebral ischemia. Moreover, the increasing use of cytokines in the immunotherapeutic treatment of various autoimmune diseases (e.g. rheumatoid arthritis) and cancers prompted us to consider the potential role of central processes in subserving the mood-related side-effects elicited by these treatments. Finally, a single administration of TNF-α has been shown to elicit a time-dependent sensitization effect, wherein the behavioral and neurochemical responses elicited by later cytokine treatment are greatly enhanced. Thus, particular attention was devoted to the possibility that elevated levels of TNF-α, through either exogenous (e.g. immunotherapy) or endogenous (e.g. brain damage or stressors) means may sensitize neurotransmitter or second messenger pathways important for the pathology. Given the time-dependent nature of cytokine sensitization effects, the schedule of cytokine administration during immunotherapy, or the timing of cytokine up-regulation in response to traumatic or stressful events may favor the development of sensitized central processes, which may influence clinical outcome.

Keywords

cytokineTNF-α? sensitizationsicknesscorticosteronemonoaminedepressionstrokeimmunotherapy
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 14 , Issue 6 , December 2002 , pp. 322 - 335
Copyright
Copyright © Acta Neuropsychiatrica 2002

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