Interleukin-6 protects anterior horn neurons from lethal virus-induced injury

Kevin D. Pavelko, Charles L. Howe, Kristen M. Drescher, Jeff D. Gamez, Aaron J. Johnson, Tao Wei, Richard M. Ransohoff, Moses Rodriguez

Research output: Contribution to journalArticle

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Abstract

We evaluated the role of interleukin-6 (IL-6) in neuronal injury after CNS infection. IL-6- and IL-6+/+ mice of resistant major histocompatibility complex (MHC) H-2b haplotype intracerebrally infected with Theiler's virus cleared the infection normally without development of viral persistence, lethal neuronal infection, or late phase demyelination. In contrast, infection of IL-6-/- mice on a susceptible H-2q haplotype resulted in frequent deaths and severe neurologic deficits within 2 weeks of infection as compared with infected IL-6+/+ H-2q littermate controls. Morphologic analysis demonstrated dramatic injury to anterior horn neurons of IL-6-/- H-2q mice at 12 d after infection. Infectious viral titers in the CNS (brain and spinal cord combined) were equivalent between IL-6-/- H-2q and IL-6+/+ H-2q mice. In contrast, more viral RNA was detected in the spinal cord of IL-6 -/- mice compared with IL-6+/+ H-2q mice. Virus antigen was localized predominantly to anterior horn cells in infected IL-6-/- H-2q mice. IL-6 deletion did not affect the humoral response directed against virus, nor did it affect the expression of CD4, CD8, MHC class I, or MHC class II in the CNS. Importantly, IL-6 was expressed by astrocytes of infected IL-6+/+ mice but not in astrocytes of IL-6-/- mice or uninfected IL-6+/+ mice. Furthermore, expression of various chemokines was robust at 12 d after infection in both H-2b and H-2q IL-6-/- mice, indicating that intrinsic CNS inflammatory responses did not depend on the presence of IL-6. Finally, in vitro analysis of virus-induced death in neuroblastoma-spinal cord-34 motor neurons and primary anterior horn cell neurons showed that IL-6 exerted a neuroprotective effect. These data support the hypothesis that IL-6 plays a critical role in protecting specific populations of neurons from irreversible injury.

Original languageEnglish
Pages (from-to)481-492
Number of pages12
JournalJournal of Neuroscience
Volume23
Issue number2
StatePublished - Jan 15 2003

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Anterior Horn Cells
Interleukin-6
Viruses
Wounds and Injuries
Infection
Major Histocompatibility Complex
Spinal Cord
Astrocytes
Haplotypes
Theilovirus
Viral RNA
Motor Neurons
Demyelinating Diseases
Neuroprotective Agents
Virus Diseases
Neurologic Manifestations
mouse interleukin-6
Neuroblastoma
Chemokines

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Pavelko, K. D., Howe, C. L., Drescher, K. M., Gamez, J. D., Johnson, A. J., Wei, T., ... Rodriguez, M. (2003). Interleukin-6 protects anterior horn neurons from lethal virus-induced injury. Journal of Neuroscience, 23(2), 481-492.

Interleukin-6 protects anterior horn neurons from lethal virus-induced injury. / Pavelko, Kevin D.; Howe, Charles L.; Drescher, Kristen M.; Gamez, Jeff D.; Johnson, Aaron J.; Wei, Tao; Ransohoff, Richard M.; Rodriguez, Moses.

In: Journal of Neuroscience, Vol. 23, No. 2, 15.01.2003, p. 481-492.

Research output: Contribution to journalArticle

Pavelko, KD, Howe, CL, Drescher, KM, Gamez, JD, Johnson, AJ, Wei, T, Ransohoff, RM & Rodriguez, M 2003, 'Interleukin-6 protects anterior horn neurons from lethal virus-induced injury', Journal of Neuroscience, vol. 23, no. 2, pp. 481-492.
Pavelko KD, Howe CL, Drescher KM, Gamez JD, Johnson AJ, Wei T et al. Interleukin-6 protects anterior horn neurons from lethal virus-induced injury. Journal of Neuroscience. 2003 Jan 15;23(2):481-492.
Pavelko, Kevin D. ; Howe, Charles L. ; Drescher, Kristen M. ; Gamez, Jeff D. ; Johnson, Aaron J. ; Wei, Tao ; Ransohoff, Richard M. ; Rodriguez, Moses. / Interleukin-6 protects anterior horn neurons from lethal virus-induced injury. In: Journal of Neuroscience. 2003 ; Vol. 23, No. 2. pp. 481-492.
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