Interleukin-10 in the brain

Klemen Strle, Jian Hua Zhou, Wen Hong Shen, Suzanne R. Broussard, Rodney W. Johnson, Gregory G. Freund, Robert Dantzer, Keith W. Kelley

Research output: Contribution to journalReview articlepeer-review


Interleukin (IL)-10 is synthesized in the central nervous system (CNS) and acts to limit clinical symptoms of stroke, multiple sclerosis, Alzheimer's disease, meningitis, and the behavioral changes that occur during bacterial infections. Expression of IL-10 is elevated during the course of most major diseases in the CNS and promotes survival of neurons and all glial cells in the brain by blocking the effects of proapoptotic cytokines and by promoting expression of cell survival signals. Stimulation of IL-10 receptors regulates numerous life- or death-signaling pathways - including Jak1/Stat3, PI 3-kinase, MAPK, SOCS, and NF-κB - ultimately promoting cell survival by inhibiting both ligand- and mitochondrial-induced apoptotic pathways. IL-10 also limits inflammation in the brain; it does so by three major pathways: (1) reducing synthesis of proinflammatory cytokines, (2) suppressing cytokine receptor expression, and (3) inhibiting receptor activation. Finally, IL-10 induces anergy in brain-infiltrating T cells by inhibiting cell signaling through the costimulatory CD28-CD80/86 pathway. The multiple functions of IL-10 in the brain will create new and intriguing vistas that will promote a better understanding of neurodegenerative diseases. These discoveries could lead to development of innovative approaches for the use of anti-inflammatory cytokines in major debilitating diseases of the CNS.

Original languageEnglish (US)
Pages (from-to)427-449
Number of pages23
JournalCritical Reviews in Immunology
Issue number5
StatePublished - 2001


  • Brain
  • Cytokines
  • IL-10 receptor
  • Inflammation
  • Neurodegeneration
  • Receptor signaling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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