Induction of proinflammatory molecules in mice with amyotrophic lateral sclerosis: no requirement for proapoptotic interleukin-1beta in neurodegeneration

Ann Neurol. 2001 Nov;50(5):630-9. doi: 10.1002/ana.1256.


Recent studies have demonstrated the activation of caspase-1 and caspase-3 in mice expressing mutant superoxide dismutase 1 (SOD1), models of amyotrophic lateral sclerosis. Caspase-1 converts the prointerleukin-1beta into a potent proinflammatory molecule involved in the innate immune response and in neurodegenerative diseases. We report on the chronic expression of interleukin-1beta mRNA in the spinal cord of SOD1G37R mice, together with robust mRNA expression for the nuclear factor-kappaB (NF-kappaB) inhibitor IkappaBalpha, for other proinflammatory cytokines and chemokines (interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1) and for the toll-like receptor TLR2 involved in innate immunity. To further assess the interleukin-1beta contribution to neurodegeneration, we generated mice expressing SOD1G37R in a context of interleukin-1beta gene knockout. Surprisingly, the absence of interleukin-1beta had no effect on the life span of SOD1G37R mice, nor on the extent of motor axon degeneration at age 7 and 10 months. Whereas neither compensatory induction of the interleukin-1alpha mRNA nor increases in mRNA levels for IkappaBalpha, tumor necrosis factor-alpha and macrophage chemoattractant protein-1 occurred as a result of interleukin-1beta gene disruption, enhanced levels of TLR2 mRNA were detected in SOD1G37R mice lacking interleukin-1beta. We conclude that interleukin-1beta does not directly contribute to motor neuron degeneration in SOD1G37R mice, but it may act as a modulator of the innate immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / pathology
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Animals
  • Apoptosis*
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Drosophila Proteins*
  • Gene Expression Regulation
  • I-kappa B Proteins*
  • Immunity, Innate
  • Interleukin-1 / deficiency
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Neurologic Mutants
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • NF-KappaB Inhibitor alpha
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase-1
  • Survival Rate
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Chemokine CCL2
  • DNA-Binding Proteins
  • Drosophila Proteins
  • I-kappa B Proteins
  • Interleukin-1
  • Interleukin-6
  • Membrane Glycoproteins
  • Nfkbia protein, mouse
  • RNA, Messenger
  • Receptors, Cell Surface
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1