Role of antifibrotic cytokine interferon-gamma in the prevention of postlaminectomy peridural fibrosis in rats.
OBJECTIVE
Extensive peridural fibrosis after spinal surgery may be the underlying cause of failed-back syndrome in some cases. There is increasing evidence that generation of specific cytokine patterns by immune and structural cells and interactions among these cells mediate many of the key events involved in fibrogenesis. Interferon-gamma (IFN-gamma) has several potential antifibrotic actions, including inhibition of fibroblast proliferation and collagen deposition, promotion of fibroblast apoptosis, and inhibition of production and action of the fibrogenic cytokine, transforming growth factor-beta. We conducted a study to determine the effectiveness of IFN-gamma in preventing postlaminectomy peridural fibrosis in rats. To the best of our knowledge, this is the first study testing immunotherapy in peridural fibrosis. Type 2 cytokine hypothesis of fibrogenesis is emphasized.


METHODS
Laminectomies were performed in 30 rats. We administered 2000 U/d IFN-gamma, 20,000 U/d IFN-gamma, or 0.2 ml/d saline to the laminectomy site through a silicone catheter for 3 days in blinded fashion. The amount of scar tissue, fibroblast density, inflammatory cell density, arachnoidal involvement, and bone regeneration were analyzed histologically.


RESULTS
Histopathological examination showed a significantly reduced amount of scar tissue and fibroblast density in the low-dose IFN-gamma group compared with the control and high-dose IFN-gamma groups. A significant increase was detected in inflammatory cell density in the high-dose IFN-gamma group compared with the control and low-dose IFN-gamma groups.


CONCLUSIONS
Cytokines play a critical role in wound healing, tissue repair, and fibrogenesis. This study suggests that topical application of low-dose IFN-gamma is an effective and safe method of preventing peridural fibrosis, but further studies with different doses, durations, and intervals are required to achieve better results.
Emmez
Hakan
H
Department of Neurosurgery, Gazi University Faculty of Medicine, Besevler, Turkey. hakanemmez@hotmail.com
Kardes
Ozgur
O
Dogulu
Fikret
F
Kurt
Gokhan
G
Memis
Leyla
L
Baykaner
M Kemali
MK
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004388:Dura Mater / Q000473:pathology*; D005355:Fibrosis / Q000209:etiology / Q000517:prevention & control; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use*; D007796:Laminectomy / Q000009:adverse effects*; D008159:Lumbar Vertebrae; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D014945:Wound Healing
D000998:Antiviral Agents; D011994:Recombinant Proteins; D007371:Interferon-gamma