Purine anti-metabolite attenuates nuclear factor κB and related pro-inflammatory cytokines in experimental vasospasm.

Abstract

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. 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. 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. 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.