title: Interleukin-6 Deficiency Does Not Affect Motor Neuron Disease Caused by Superoxide Dismutase 1 Mutation.
abstract: OBJECTIVE
  Amyotrophic Lateral Sclerosis (ALS) is an adult-onset, progressive, motor neuron degenerative disease. Recent evidence indicates that inflammation is associated with many neurodegenerative diseases including ALS. Previously, abnormal levels of inflammatory cytokines including IL-1β, IL-6 and TNF-α were described in ALS patients and/or in mouse ALS models. In addition, one study showed that blocking IL-1β could slow down progression of ALS-like symptoms in mice. In this study, we examined a role for IL-6 in ALS, using an animal model for familial ALS.
  
  
  METHODS
  Mice with mutant SOD1 (G93A) transgene, a model for familial ALS, were used in this study. The expression of the major inflammatory cytokines, IL-6, IL-1β and TNF-α, in spinal cords of these SOD1 transgenic (TG) mice were assessed by real time PCR. Mice were then crossed with IL-6(-/-) mice to generate SOD1TG/IL-6(-/-) mice. SOD1 TG/IL-6(-/-) mice (n = 17) were compared with SOD1 TG/IL-6(+/-) mice (n = 18), SOD1 TG/IL-6(+/+) mice (n = 11), WT mice (n = 15), IL-6(+/-) mice (n = 5) and IL-6(-/-) mice (n = 8), with respect to neurological disease severity score, body weight and the survival. We also histologically compared the motor neuron loss in lumber spinal cords and the atrophy of hamstring muscles between these mouse groups.
  
  
  RESULTS
  Levels of IL-6, IL-1β and TNF-α in spinal cords of SOD1 TG mice was increased compared to WT mice. However, SOD1 TG/IL-6(-/-) mice exhibited weight loss, deterioration in motor function and shortened lifespan (167.55 ± 11.52 days), similarly to SOD1 TG /IL-6(+/+) mice (164.31±12.16 days). Motor neuron numbers and IL-1β and TNF-α levels in spinal cords were not significantly different in SOD1 TG /IL-6(-/-) mice and SOD1 TG /IL-6 (+/+) mice.
  
  
  CONCLUSIONS
  These results provide compelling preclinical evidence indicating that IL-6 does not directly contribute to motor neuron disease caused by SOD1 mutations.
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871 Japan.|Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Han
authors.affiliation: Laboratory of Immune Regulation, IFReC Research Building, Osaka University 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Barry
authors.initials: B
authors.lastname: Ripley
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Serada
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Naka
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Fujimoto
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000172:deficiency*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics; D016472:Motor Neuron Disease / Q000235:genetics* / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D013116:Spinal Cord / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1