Utility of serum cytokines as biomarkers for ischemic stroke in translational research

Purpose: The inflammatory response plays an important role in the pathogenesis of ischemic stroke. Many clinical studies use serum as a surrogate measure of the inflammation process in the brain. In this investigation we aimed at comparing the levels of four major cytokines (IL-1α, IL-6, IL-10 & TNF- α) in the rat brain and serum after experimental ischemic stroke.

Methods: 25 Wistar rats were subjected to either temporary (tMCAO, n=11) for 3 hours, permanent (pMCAO, n=11) middle cerebral artery occlusion, or sham (n= 3) and the animals were euthanized at either 24 or 72 hours after the onset of ischemia. Brain tissue and serum were collected and the levels of cytokines were assayed using a multiplex array system (Bio-Plex 200). Cytokine levels in each hemisphere were compared to sham operated animals.

Results: At 24 hours after tMCAO, inflammatory cytokines (IL-1α, IL-6 & TNF-α) were significantly increased in the ischemic brain hemisphere (p<0.05) as compared to shams. This increase subsided after 72 hours. In the serum, cytokine levels significantly increased only after 72 hours of both tMCAO & pMCAO (p<0.05). At 24 hours, the anti-inflammatory IL-10 was significantly higher in the contralesional versus stroked side. However, IL-10 increased significantly in the stroked hemispheres of both pMCAO and tMCAO groups 72 hours after MCAO (p<0.05). A similar pattern was observed in the serum.

Conclusion: Changes in inflammatory cytokines occur earlier in the brain than in the serum and are exaggerated when reperfusion occurs. Serum cytokines reflect both the inflammatory and anti-inflammatory response to focal cerebral ischemia. In order to more accurately assess brain inflammation, both inflammatory and anti-inflammatory cytokines should be quantified.