A neuromodulatory role of interleukin-1β in the hippocampus

It is widely accepted that interleukin-1β (IL-1β), a cytokine produced not only by immune cells but also by glial cells and certain neurons influences brain functions during infectious and inflammatory processes. It is still unclear, however, whether IL-1 production is triggered under nonpathological conditions during activation of a discrete neuronal population and whether this production has functional implications. Here, we show in vivo and in vitro that IL-1β gene expression is substantially increased during long-term potentiation of synaptic transmission, a process considered to underlie certain forms of learning and memory. The increase in gene expression was long lasting, specific to potentiation, and could be prevented by blockade of potentiation with the N-methyl-d-aspartate (NMDA) receptor antagonist, (±)-2-amino-5-phosphonopentanoic acid (AP-5). Furthermore, blockade of IL-1 receptors by the specific interleukin-1 receptor antagonist (IL-1ra) resulted in a reversible impairment of long-term potentiation maintenance without affecting its induction. These results show for the first time that the production of biologically significant amounts of IL-1β in the brain can be induced by a sustained increase in the activity of a discrete population of neurons and suggest a physiological involvement of this cytokine in synaptic plasticity.

[1]  J. Sarvey,et al.  Blockade of norepinephrine-induced long-lasting potentiation in the hippocampal dentate gyrus by an inhibitor of protein synthesis , 1985, Brain Research.

[2]  D. Baly,et al.  Interleukin‐1 stimulates glucose transport in rat adipose cells , 1990 .

[3]  C. Pert,et al.  Visualization and characterization of interleukin 1 receptors in brain. , 1987, Journal of immunology.

[4]  B. Hogan,et al.  Manipulating the mouse embryo: A laboratory manual , 1986 .

[5]  K. Schauenstein,et al.  NEUROIMMUNOMODULATION VIA LIMBIC STRUCTURES — THE NEUROANATOMY OF PSYCHOIMMUNOLOGY , 1997, Progress in Neurobiology.

[6]  M. Labow,et al.  Molecular Cloning and Characterization of a Second Subunit of the Interleukin 1 Receptor Complex (*) , 1995, The Journal of Biological Chemistry.

[7]  M. Krug,et al.  Anisomycin blocks the late phase of long-term potentiation in the dentate gyrus of freely moving rats , 1984, Brain Research Bulletin.

[8]  E. Kandel,et al.  D1/D5 receptor agonists induce a protein synthesis-dependent late potentiation in the CA1 region of the hippocampus. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[9]  S. Kanba,et al.  Interleukin-1 beta augments release of norepinephrine, dopamine, and serotonin in the rat anterior hypothalamus , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  A. Arimura,et al.  Interleukin-1 stimulates ACTH release by an indirect action which requires endogenous corticotropin releasing factor. , 1987, Endocrinology.

[11]  Y. Kiso,et al.  Interleukin-1 beta inhibits long-term potentiation in the CA3 region of mouse hippocampal slices. , 1990, European journal of pharmacology.

[12]  H. Besedovsky,et al.  Immune-neuro-endocrine interactions: facts and hypotheses. , 1996, Endocrine reviews.

[13]  J. Licinio,et al.  Interleukin (IL) 1beta, IL-1 receptor antagonist, IL-10, and IL-13 gene expression in the central nervous system and anterior pituitary during systemic inflammation: pathophysiological implications. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[14]  K. McIntyre,et al.  Insertion of a Structural Domain of Interleukin (IL)-1β Confers Agonist Activity to the IL-1 Receptor Antagonist , 1995, The Journal of Biological Chemistry.

[15]  H. Besedovsky,et al.  Antidiabetic effects of interleukin 1. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[16]  N. Rothwell,et al.  Cytokines and the nervous system II: actions and mechanisms of action , 1995, Trends in Neurosciences.

[17]  C. Dinarello,et al.  Biologic basis for interleukin-1 in disease. , 1996, Blood.

[18]  T. Dj,et al.  Inflammatory cytokines stimulate glucose uptake and glycolysis but reduce glucose oxidation in human dermal fibroblasts in vitro. , 1992 .

[19]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[20]  C. Dinarello,et al.  Interleukin-1 augments gamma-aminobutyric acidA receptor function in brain. , 1991, Molecular pharmacology.

[21]  A. Arimura,et al.  Identification of a high-affinity receptor for interleukin-1 beta in rat brain. , 1988, Biochemical and biophysical research communications.

[22]  C. Newton,et al.  Spatial Learning Impairment in Mice Infected with Legionella pneumophila or Administered Exogenous Interleukin-1-β , 1995, Brain, Behavior, and Immunity.

[23]  U. Frey,et al.  Synaptic tagging and long-term potentiation , 1997, Nature.

[24]  P. Sawchenko,et al.  Type 1 interleukin‐1 receptor in the rat brain: Distribution, regulation, and relationship to sites of IL‐1–induced cellular activation , 1995, The Journal of comparative neurology.

[25]  A. Dunn,et al.  Systemic interleukin-1 administration stimulates hypothalamic norepinephrine metabolism parallelling the increased plasma corticosterone. , 1988, Life sciences.

[26]  J. Sarvey,et al.  Blockade of long-term potentiation in rat hippocampal CA1 region by inhibitors of protein synthesis , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[27]  M. Manthorpe,et al.  Synthetic NGF peptide derivatives prevent neuronal death via a p75 receptor‐dependent mechanism , 1997, Journal of neuroscience research.

[28]  H. Besedovsky,et al.  Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1. , 1987, Science.

[29]  G. Siggins,et al.  Interleukin 1β inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus , 1993, Brain Research.

[30]  M R Rosenzweig,et al.  Aspects of the search for neural mechanisms of memory. , 1996, Annual review of psychology.

[31]  J. J. O'Connor,et al.  Interleukin-1β (IL-1β) and tumour necrosis factor (TNF) inhibit long-term potentiation in the rat dentate gyrus in vitro , 1996, Neuroscience Letters.

[32]  R. Dantzer,et al.  Sickness behavior as a new target for drug development. , 1992, Trends in pharmacological sciences.

[33]  C Chen,et al.  Molecular genetic analysis of synaptic plasticity, activity-dependent neural development, learning, and memory in the mammalian brain. , 1997, Annual review of neuroscience.

[34]  E. Kandel,et al.  Mice Expressing Activated CaMKII Lack Low Frequency LTP and Do Not Form Stable Place Cells in the CA1 Region of the Hippocampus , 1996, Cell.

[35]  H. Besedovsky,et al.  Interleukin-1 induces changes in norepinephrine metabolism in the rat brain , 1988, Brain, Behavior, and Immunity.

[36]  Robert C. Malenka,et al.  Synaptic plasticity in the hippocampus: LTP and LTD , 1994, Cell.

[37]  C. Dinarello,et al.  Characterization of a subclone (D10S) of the D10.G4.1 helper T-cell line which proliferates to attomolar concentrations of interleukin-1 in the absence of mitogens. , 1989, Cytokine.

[38]  R. Sapolsky,et al.  Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor. , 1987, Science.

[39]  M. Oitzl,et al.  Interleukin-1β, but not interleukin-6, impairs spatial navigation learning , 1993, Brain Research.

[40]  K. Reymann,et al.  A post-tetanic time window for the reinforcement of long-term potentiation by appetitive and aversive stimuli. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[41]  David J. Anderson,et al.  Subregion- and Cell Type–Restricted Gene Knockout in Mouse Brain , 1996, Cell.

[42]  P. Braquet,et al.  Platelet-activating factor and cellular immune responses. , 1987, Immunology today.

[43]  L. Rawlinson,et al.  Interleukin 1 induces NF-kappa B through its type I but not its type II receptor in lymphocytes. , 1992, The Journal of biological chemistry.