In vivo and in vitro evidence supporting a role for the inflammatory cytokine interleukin-1 as a driving force in Alzheimer pathogenesis

Jin G. Sheng, Kazuhiro Ito, Robert D. Skinner, Robert E. Mrak, Cynthia R. Rovnaghi, Linda J. Van Eldik, W. Sue T. Griffin

Research output: Contribution to journalArticlepeer-review

242 Scopus citations


Interleukin-1 (IL-1), an inflammatory cytokine overexpressed in the neuritic plaques of Alzheimer's disease, activates astrocytes and enhances production and processing of β-amyloid precursor protein (β-APP). Activated astrocytes, overexpressing S100β, are a prominent feature of these neuritic plaques, and the neurite growth-promoting properties of S100β have been implicated in the formation of dystrophic neurites overexpressing β-APP in neuritic plaques. These facts collectively suggest that elevated levels of the inflammatory cytokine IL-1 drive S100β and β-APP overexpression and dystrophic neurite formation in Alzheimer's disease. To more directly assess this driver potential for IL-1, we analyzed IL-1 induction of S100β expression in vivo and in vitro, and of β-APP expression in vivo. Synthetic IL-1β was injected into the right cerebral hemispheres of 13 rats. Nine additional rats were injected with phosphate-buffered saline, and seven rats served as uninjected controls. The number of astrocytes expressing detectable levels of S100β in tissue sections from IL-1-injected brains was 1.5 fold that of either control group (p < 0.01), while tissue S100β levels were approximately threefold that of controls (p < 0.05). The tissue levels of two β-APP isoforms (approximately 130 and 135 kDa) were also significantly elevated in IL-1-injected brains (p < 0.05). C6 glioma cells, treated in vitro for 24 h with either IL-1β or IL-1α, showed significant increases in both S100β and S100β mRNA levels. These results provide evidence that IL-1 upregulates both S100β and β-APP expression, in vivo and in vitro, and support the idea that overexpression of IL-1 in Alzheimer's disease drives astrocytic overexpression of S100β, favoring the growth of dystrophic neurites necessary for evolution of diffuse amyloid deposits into neuritic β-amyloid plaques.

Original languageEnglish
Pages (from-to)761-766
Number of pages6
JournalNeurobiology of Aging
Issue number5
StatePublished - 1996

Bibliographical note

Funding Information:
This work was supported in part by NIH Grants AGI0208 (to W.S.T.G., L.J.V,E., and R.E.M.), AG12411 (to W.S.TG. and R.E.M./and NS27414 (to W.ST.G.). The authors wish to thank Drs. Laura Stanley, John Wu, and Tim Wall for their assistance with experiments, Dr. Gareth Roberts for helpful advice on the manuscript, and Ms. Pare Free for secretarial support.


  • Alzheimer's disease
  • C6 glioma cells
  • Down's syndrome
  • Interleukin-1
  • Rats
  • S100β
  • β-Amyloid precursor protein

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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