Neuroinflammation mediated by IL-1beta increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson's disease

J Neuroinflammation. 2008 Feb 27;5:8. doi: 10.1186/1742-2094-5-8.

Abstract

Background: The etiology of Parkinson's disease (PD) remains elusive despite identification of several genetic mutations. It is more likely that multiple factors converge to give rise to PD than any single cause. Here we report that inflammation can trigger degeneration of dopamine (DA) neurons in an animal model of Parkinson's disease.

Methods: We examined the effects of inflammation on the progressive 6-OHDA rat model of Parkinson's disease using immunohistochemistry, multiplex ELISA, and cell counting stereology.

Results: We show that a non-toxic dose of lipopolysaccharide (LPS) induced secretion of cytokines and predisposed DA neurons to be more vulnerable to a subsequent low dose of 6-hydroxydopamine. Alterations in cytokines, prominently an increase in interleukin-1beta (IL-1beta), were identified as being potential mediators of this effect that was associated with activation of microglia. Administration of an interleukin-1 receptor antagonist resulted in significant reductions in tumor necrosis factor-alpha and interferon-gamma and attenuated the augmented loss of DA neurons caused by the LPS-induced sensitization to dopaminergic degeneration.

Conclusion: These data provide insight into the etiology of PD and support a role for inflammation as a risk factor for the development of neurodegenerative disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antirheumatic Agents / pharmacology
  • Disease Models, Animal
  • Disease Susceptibility
  • Dopamine / physiology*
  • Female
  • Interleukin 1 Receptor Antagonist Protein / pharmacology
  • Interleukin-1beta / immunology*
  • Lipopolysaccharides / pharmacology
  • Microglia / immunology
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / epidemiology
  • Nerve Degeneration / immunology*
  • Neuritis / chemically induced
  • Neuritis / epidemiology
  • Neuritis / immunology*
  • Neuroimmunomodulation / immunology
  • Oxidopamine
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / epidemiology
  • Parkinsonian Disorders / immunology*
  • Rats
  • Rats, Sprague-Dawley
  • Risk Factors
  • Substantia Nigra / drug effects
  • Substantia Nigra / immunology
  • Sympatholytics

Substances

  • Antirheumatic Agents
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Lipopolysaccharides
  • Sympatholytics
  • Oxidopamine
  • Dopamine