Background: IP-10 is a pro-inflammatory CXC chemokine that acts as a chemo-attractant for monocytes and T cells. Prior work has shown that IP-10 levels increase after experimental stroke. IP-10 levels are correlated with degree of neurological injury; lower levels are associated with better outcome. Importantly, although nearly three quarters of strokes occur in aged people, no studies have examined IP-10 levels in aged stroke patient or animal populations. As mice and humans age, there is a progressive increase in pro-inflammatory factors circulating in the blood. Consequently, we hypothesize that aged populations will have significantly higher post-stroke IP-10 levels.
Methods: Young (2-3 months) and aged (20 months) male C57BL6 mice were subjected to 60 minutes (24hr and 28 day group) or 90 minutes (72hr group) of MCAO and randomly split into 3 groups (n=5/group). Mice were sacrificed 24hrs, 72hrs, or 28 days after sham or stroke surgery. We collected serum samples from the 24hr and 28-day group and brain samples from the 72hr group. We also collected young (37-69yrs; n=18) and aged (70yrs; n=23) human serum samples 24hrs after imaging-confirmed ischemic stroke. IP-10 levels were assessed via ELISA (mouse) and cytokine multiplex assay (human).
Results: Aged mice had significantly higher serum IP-10 levels than young mice (102.43±9.21pg/ml vs. 61.99±8.98pg/ml; p<.0001). However, there was no significant difference in either age group 24hrs after stroke. There was an interaction effect of age and stroke 72hrs after stroke, (F (1,14) =10.25, p<.006); aged stroke mice had the highest brain IP-10 levels. There was a significant increase in serum IP-10 levels in aged stroke mice compared to aged sham (45.47±5.32pg/ml vs. 23.26±0.31pg/ml; p<.03) and in aged stroke compared to young mice (45.47±5.32pg/ml vs. 15.72±2.63pg/ml; p<.005) 28 days after stroke. However, there was no difference between young stroke and sham. Lastly, in line with our animal data, serum IP-10 levels were significantly higher in aged humans (p<.02).
Conclusions: This study demonstrates that aging exacerbates post-stroke brain and serum IP-10 levels in both mice and human subjects. Blocking IP-10 may be especially beneficial in improving post stroke recovery in aged populations.