Abstract
Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFα) are proinflammatory cytokines that are constitutively expressed in healthy, adult brain where they mediate normal neural functions such as sleep. They are neuromodulators expressed by and acting on neurons and glia. IL-1 and TNFα expression is upregulated in several important diseases/disorders. Upregulation of IL-1 and/or TNFα expression, elicited centrally or systemically, propagates through brain parenchyma following specific spatio-temporal patterns. We propose that cytokine signals propagate along neuronal projections and extracellular diffusion pathways by molecular cascades that need to be further elucidated. This elucidation is a prerequisite for better understanding of reciprocal interactions between nervous, endocrine and immune systems.
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Acknowledgements
We thank E Kandel for commenting on an earlier version of this manuscript, JL Tchélingérian and F Le Saux for contributions to Figure 1 and M Passama for producing the figures. LV was a Professor of the French Academy of Sciences, Chair ELF Aquitaine while this work was done. He thanks ELF Aquitaine for support. This work was also supported by the French Foundation for Medical Research (EP001195/01 to LV), European community (BIOMED 2, CT97–2492 and TMR, CT-97-0142 to RD), French Association Against Cancer (9781 to JB), INSERM and ARSEP (to CJ).
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Vitkovic, L., Konsman, J., Bockaert, J. et al. Cytokine signals propagate through the brain. Mol Psychiatry 5, 604–615 (2000). https://doi.org/10.1038/sj.mp.4000813
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