¹CNRS-INSERM Centre de Pharmacologie-Endocrinologie, Montpellier, France

²INRA-INSERM U-394, Institut Francois Magendie, Bordeaux, France

³INSERM U-495, Hôpital de la Salpêtrière, Paris, France

Correspondence to: L Vitkovic PhD, 7809 Moorland Lane, Bethesda, MD 20814, USA. E-mail: vitkovic@hotmail.com

Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF) 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 TNF expression is upregulated in several important diseases/disorders. Upregulation of IL-1 and/or TNF 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. Molecular Psychiatry (2000) 5, 604-615.

cytokines; IL-1; TNF; brain; pathophysiology