title: Purine anti-metabolite attenuates nuclear factor κB and related pro-inflammatory cytokines in experimental vasospasm.
abstract: BACKGROUND
  Increased nuclear factor κB (NF-κB) bioexpression, as well as TNF-α, IL-1β and IL-6 levels, were observed after aneurysmal subarachnoid hemorrhage (SAH). It is of interest to investigate the effect of 6-mercaptopurine (6-mp) on cytokines/NF-κB in this SAH model.
  
  
  METHODS
  A rodent double-hemorrhage SAH model was employed. Serum and cerebrospinal fluid (CSF) samples were collected to examine IL-1, IL-6 and TNF-α levels. NF-κB subunit p65 and its inhibitor of nuclear factor κB (IκB) were examined (by Western blot). TNF-α was used to induce the phosphorylation of IκB in the presence or absence of 6-mp.
  
  
  RESULTS
  Nuclear NF-κB subunit p65/IκB kinase in the basilar artery was over-expressed, and cytokines was notably increased in the SAH groups, compared with the controls (P < 0.01). In the 6-mp SAH group, obvious reduction was observed in NF-κB subunit p65 (nuclei) (P < 0.01). Treatment with 6-mp significantly reduced IL-1β and TNF-α levels to those of the healthy control. 6-Mercaptopurine also significantly increased the level of IκB in the TNF-α-stimulated SAH rats.
  
  
  CONCLUSIONS
  Through inhibiting IκB bioexpression, 6-mp decreases NF-κB-related IL-1β, IL-6, and TNF-α in the presence of SAH. The study suggests 6-mp exerts vascular anti-inflammatory properties through inhibiting IκB kinase and subsequently blocks bio-activation of NF-κB and related cytokines, which may contribute to its antivasospastic effect in animals subjected to SAH.
authors.affiliation: Department of Surgery, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. cjc4b@pchome.com.tw
authors.forename: Chih-Zen
authors.initials: CZ
authors.lastname: Chang
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Wu
authors.forename: Chih-Long
authors.initials: CL
authors.lastname: Lin
authors.forename: Shiuh-Lin
authors.initials: SL
authors.lastname: Hwang
authors.forename: Aij-Lie
authors.initials: AL
authors.lastname: Kwan
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011687:Purines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020301:Vasospasm, Intracranial / Q000378:metabolism / Q000601:surgery*
chemical_list: D016207:Cytokines; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D011687:Purines; D000072000:NF-KappaB Inhibitor alpha; C030985:purine