Cytokine activity contributes to induction of inflammatory cytokine mRNAs in spinal cord following contusion

Jonathan Z. Pan, Li Ni, Ajeet Sodhi, Ann Aguanno, Wise Young, Ronald Hart

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

Abstract

Injury of the spinal cord leads to an inflammatory tissue response, probably mediated in part by cytokines. Because a common therapy for acute spinal cord injury is the use of an antiinflammatory synthetic glucocorticoid (methylprednisolone), we sought to determine mechanisms contributing to inflammation shortly after acute injury. Cytokine mRNAs [interleukin (IL)-1α, IL-1β, tumor necrosis factor (TNF)-α, and IL-6] were increased during the first 2 hr following weight-drop compression injury by RNase protection assay, prior to the reported appearance of circulating lymphocytes. This immediate pattern of cytokine mRNA induction could be replicated in cultured, explanted spinal cord slices but not in whole blood of injured animals, which is consistent with a tissue source of cytokine mRNAs. Western blotting detected IL-1β-like immunoreactivity released into culture medium following explantation and pro-IL-1β-like immunoreactivity in freshly dissected spinal cord tissue. Pharmacologically blocking IL-1 and TNF-α receptors significantly reduced expression of IL-1α, IL-1β, and TNF-α mRNAs. Finally, mice lacking both IL-1 and TNF-α receptors exhibited diminished induction of TNF-α, IL-6, and IL-1ra mRNAs following injury. Therefore, we conclude that contusion injury induces an immediate release of cytokines, which then contributes to the induction of cytokine mRNAs.

Original languageEnglish (US)
Pages (from-to)315-322
Number of pages8
JournalJournal of Neuroscience Research
Volume68
Issue number3
DOIs
StatePublished - May 1 2002

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Keywords

  • Cytokine
  • Gene knockout
  • Inflammation
  • Methylprednisolone
  • Spinal cord injury

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