Interleukin-6 Deficiency Does Not Affect Motor Neuron Disease Caused By Superoxide Dismutase 1 Mutation

Background & AimAmyotrophic Lateral Sclerosis (ALS) is an adult-onset, progressive, motor neuron degenerative disease. Recent evidence indicates that inflammation is associated with many neuro-degenerative diseases including ALS. Previously, abnormal levels of inflammatory cytokines including IL-1 beta, IL-6 and TNF-alpha were described in ALS patients and/or in mouse ALS models. In addition, one study showed that blocking IL-1 beta 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.MethodsMice 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-1 beta and TNF-alpha, 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.ResultsLevels of IL-6, IL-1 beta and TNF-alpha 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-1 beta and TNF-alpha levels in spinal cords were not significantly different in SOD1 TG/IL-6(-/-) mice and SOD1 TG/IL-6 (+/+) mice.ConclusionThese results provide compelling preclinical evidence indicating that IL-6 does not directly contribute to motor neuron disease caused by SOD1 mutations.