Introduction: An improper immune response has been shown to increase mortality following acute ischemic stroke (AIS), and targeting the immune system may offer a critical, novel treatment option in AIS. Recently, several immune-modulating agents, such as neutrophil inhibitory factor (UK-279, 276) showed promise in preclinical AIS models; however, either failed or were detrimental in clinical trials. One potential reason for their failure may be an improper time of administration, due to a lack of characterization of a healthy versus a detrimental peripheral immune profile following AIS. The aim of this study is to characterize the pattern of peripheral neutrophil and lymphocyte expression and neutrophil-lymphocyte ratio (NLR) following AIS.
Hypothesis: We hypothesized that patients with mild AIS or good functional outcome following AIS will display an elevated NLR from 0-48 hours due to increased neutrophil activation, followed by a reduction in NLR from 48-96 hours due to an increase in lymphocyte activation.
Methods: We analyzed data from 300 AIS patients for this study. White blood cell differentials were used to record neutrophil and lymphocyte percentages at several time points during hospitalization and to calculate NLR. AIS patients were grouped by severity using their National Institutes of Health Stroke Score (NIHSS) at admission and by functional outcome using their Modified Rankin Scale (MRS) at discharge.
Results: Regardless of severity or outcome, patients have an elevated neutrophil percentage from 0-48 hours following AIS. From 48-96 hours following AIS, patients with mild AIS or MRS 0-2 have a significant decrease in neutrophil percentage, with a concordant increase in lymphocyte percentage compared to severe AIS patients. Further, NLR at discharge is significantly higher in severe AIS patients or patients with MRS>2 (p=0.014).
Conclusion: In conclusion, our study is the first to describe the patterns of peripheral neutrophil and lymphocyte expression in the acute phase of AIS. These findings may shed light on the failure of UK-279,276 in clinical trial. This study also provides support for the use of the NLR as a prognostic marker, especially at ~48 hours following AIS, compared to the traditional assessment at admission.