Pro-inflammatory cytokine network in peripheral inflammation response to cerebral ischemia

The key circulating pro-inflammatory cytokines and their interaction in peripheral inflammation after acute cerebral ischemia are poorly understood. CD40L, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-17 and TNF-α were determined using multi-ELISA kit in stroke patients within 72 h of an acute ischemic attack. Leukocyte mRNAs were determined using real-time polymerase chain reactions (PCR). Stroke severity and clinical outcomes were evaluated by National Institutes of Health Stroke Scores (NIHSS) and modified Rankin Scale (mRS). Plasma/mRNA cytokine interactions were analyzed using the Bayesian network learning procedure. Compared to controls, stroke patients had higher IL-6, IL-8 and TNFα protein in plasma and lower IL-6, IL-8, TNFα, IL-1α, and IL-1β mRNA in leukocyte within 72 h after stroke. However, only the elevation of IL-6 correlated with the severity and prognosis of their stroke. This was associated with a decreased IL-6 mRNA in leukocyte. Further study showed that Bayesian network analysis revealed that changes in the other cytokines were subsequent to IL-6 leukocyte cytokine RNA. The change of other cytokines in plasma proteins after ischemic brain injury appeared secondary to IL-6. Pro-inflammatory cytokines up-regulation in plasma and compensatory immunity depression in leukocyte involve in peripheral inflammation response to cerebral ischemia. IL-6 appears to be the key mediator of circulating pro-inflammatory cytokines network.