Early attenuation of lesional interleukin-16 up-regulation by dexamethasone and FTY720 in experimental traumatic brain injury

Neuropathol Appl Neurobiol. 2008 Jun;34(3):330-9. doi: 10.1111/j.1365-2990.2007.00893.x. Epub 2007 Nov 5.

Abstract

Aims: Interleukin-16 (IL16) is an immunomodulatory cytokine, which induces lymphocyte migration, expression of proinflammatory IL1 beta, IL6 and tumour necrosis factor-alpha, and modulates apoptosis. IL16 expression has been observed in several central nervous system diseases and may play a role in promoting inflammatory responses. Inflammation contributes considerably to secondary injury following traumatic brain injury (TBI). The aim of this study was to investigate early IL16 expression following experimental TBI and the effects of dexamethasone and FTY720 on early expression of IL16 in TBI rats.

Methods: Rat TBI was induced using an open-skull weight-drop model. IL16 expression was studied by immunohistochemistry. TBI rats received an intraperitoneal injection of dexamethasone (1 mg/kg in 1 ml saline), FTY720 (1 mg/kg in 1 ml saline) or saline (1 ml) on Day 0 and Day 2 immediately after surgery.

Results: Significant up-regulation of IL16 was seen as early as 24 h post TBI. Double-staining experiments, together with morphological classification, revealed a multicellular origin of IL16, including activated microglia/macrophages (about 85%), astrocytes (about 8%), neurones (about 5%) and granulocytes. Following peripheral administration of dexamethasone and FTY720, attenuated numbers of IL16(+) cells were observed on Days 1 and 2 but not on Day 4 post TBI for dexamethasone and on Day 4 but not earlier for FTY720 respectively.

Conclusions: Our observations reveal that dexamethasone and FTY720 have different but complementary effects on reduction of early IL16 expression following TBI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology
  • Brain Injuries / physiopathology
  • Dexamethasone / pharmacology*
  • Fingolimod Hydrochloride
  • Functional Laterality
  • Immunohistochemistry
  • Interleukin-16 / biosynthesis*
  • Macrophages / metabolism
  • Propylene Glycols / pharmacology*
  • Rats
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Up-Regulation

Substances

  • Anti-Inflammatory Agents
  • Interleukin-16
  • Propylene Glycols
  • Dexamethasone
  • Fingolimod Hydrochloride
  • Sphingosine