Adenovirus-mediated interleukin-2 gene therapy of nociception.
The effect of adenovirus-mediated interleukin-2 (IL-2) gene on rat basal nociceptive response and chronic neuropathic pain was explored. The paw withdrawal latency induced by radiant heat was used to evaluate the antinociceptive effect of adenovirus type 5 (Ad5) and Ad5-IL-2. The results showed that intrathecal delivery of Ad5-IL-2 exhibited obvious antinociceptive effects on basal nociceptive response and chronic neuropathic pain, which were maintained for 3 and 4 weeks, respectively. This suggested that the antinociceptive effect of Ad5-IL-2 on chronic neuropathic pain was greater than its effect on basal nociceptive response. Human IL-2 mRNA was detected by in situ hybridization in the spinal pia mater and parenchyma of the lumbar, sacral, thoracic and cervical regions, and gray matter had higher level of IL-2 expression than white matter. These data demonstrated that the IL-2 gene was transfected into spinal cord regions relevant to pain modulation. The expressed IL-2 protein profile in spinal cord detected by enzyme-linked immunosorbent assay coincided almost exactly with its antinociceptive effect. This supported the hypothesis that the therapeutic effect of IL-2 gene was related to IL-2 protein expression. The study indicates that intrathecal delivery of adenovirus-mediated IL-2 gene has a relatively long antinociceptive effect.
Yao
M Z
MZ
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Gu
J F
JF
Wang
J H
JH
Sun
L Y
LY
Liu
H
H
Liu
X Y
XY
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D017403:In Situ Hybridization / Q000379:methods; D007278:Injections, Spinal; D007376:Interleukin-2 / Q000235:genetics*; D009619:Nociceptors / Q000502:physiology; D059408:Pain Management; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000276:immunology
D007376:Interleukin-2; D012333:RNA, Messenger