Effect of neutralization of rat interleukin 6 bioactivity on inducible nitric oxide synthase up-regulation and cerebral ischemic damage

Neurol Res. 2009 Sep;31(7):714-20. doi: 10.1179/174313209X380892. Epub 2008 Nov 25.


Objectives: Our aim was to investigate whether neutralization of rat interleukin 6 (IL-6) bioactivity attenuates inducible nitric oxide synthase (iNOS) up-regulation and ameliorates cerebral ischemic damage in a model of focal central nervous system (CNS) ischemia.

Methods: Seventy rats were randomly allocated to groups: Group I (n=10) consisted of normal controls; Group II (n=20) underwent surgical exposure of the middle cerebral artery but no cauterization; the remaining 40 rats were subjected to middle cerebral artery occlusion. Immediately after occlusion, each of these 40 rats was randomly assigned to either the occlusion-only group (Group III, n=20) or the occlusion plus IL-6 antibody treatment group (Group IV, n=20). Half of the rats from each of Groups II, III and IV were eternized at 24 hours and the other half at 72 hours. The samples were used for iNOS immunohistochemistry and structural analysis.

Results: A single dose of the antibody had no effect on structural changes and iNOS at 24 hours after occlusion. However, administering three doses of the antibody resulted in markedly decreased quantitative and qualitative levels of iNOS-positive stained cells and milder subcellular damage compared with the findings in the occlusion-only group at 72 hours after occlusion.

Discussion: Our findings prove that IL-6 bioactivity is one of the pathological events that trigger the induction of iNOS in the process of CNS ischemic injury. It appears that there may be therapeutic value in neutralization of IL-6 bioactivity to attenuate iNOS up-regulation and ameliorate cerebral ischemic damage in long-term recovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology*
  • Brain / drug effects
  • Brain / enzymology
  • Brain / metabolism*
  • Brain / pathology*
  • Brain / ultrastructure
  • Disease Models, Animal
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / enzymology
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / physiopathology*
  • Interleukin-6 / immunology*
  • Male
  • Microscopy, Electron, Transmission
  • Nitric Oxide Synthase Type II / metabolism*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Statistics, Nonparametric
  • Up-Regulation / drug effects*


  • Antibodies
  • Interleukin-6
  • Nitric Oxide Synthase Type II