Early attenuation of lesional interleukin-16 up-regulation by dexamethasone and FTY720 in experimental traumatic brain injury.
OBJECTIVE
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.
Zhang
Z
Z
Institute of Brain Research, University of Tuebingen, Tuebingen, Germany. zhangzhiren@yahoo.com
Fauser
U
U
Schluesener
H J
HJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology*; D000068876:Fingolimod Hydrochloride; D007839:Functional Laterality; D007150:Immunohistochemistry; D019410:Interleukin-16 / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D019410:Interleukin-16; D011409:Propylene Glycols; D003907:Dexamethasone; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine