Higher Plasma Fractalkine Is Associated With Better 6-Month Outcome From Ischemic Stroke

Abstract

Background and Purpose Fractalkine (CX3CL1) is a unique chemokine that is constitutively expressed on neurons where it serves as an adhesion molecule for lymphocytes and monocytes. CX3CL1 may also be cleaved from the surface of these cells and enter the circulation to act as a traditional chemokine. CX3CL1 could thus influence the inflammatory response following stroke. We hypothesized that patients with higher plasma CX3CL1 after stroke would have a more robust inflammatory response and experience worse outcome. Methods Plasma CX3CL1 concentrations were assessed in 85 patients who were part of a larger study evaluating immune responses following ischemic stroke; CX3CL1 values were available from day 1 to day 180 after stroke onset. CX3CL1 was correlated to measures of inflammation and its effect on outcome assessed. Results At 1 day after stroke, CX3CL1 was lower in patients with severe strokes. At 180 days after stroke, CX3CL1 concentrations were lower in patients with poor outcome. The association of CX3CL1 and outcome at 180 days was independent of initial stroke severity. Plasma CX3CL1 at 180 days was inversely associated with systemic markers of inflammation, including white blood cell counts and high sensitivity C reactive protein. Conclusions In contrast to our original hypothesis, lower concentrations of CX3CL1 are associated with worse stroke outcome. In light of recent studies suggesting an immunomodulatory and neuroprotective role for CX3CL1 in a variety of neurodegenerative diseases, a therapeutic role for CX3CL1 in stroke recovery should be considered.

Effect of Aspirin on Fractalkine in Rats with Pulmonary Embolism

“…FKN together with its receptor on the endothelial cells is potent enough to capture the white blood cells to adhere closely to vascular endothelium even in the high blood flow [14]. When the aorta is full of inflammatory cells gathered by FKN, it will play a role in the pathogenesis of some diseases, such as acute lung injury, pulmonary hypertension [15], and ischemic stroke [16]. .…”

Modulating neurotoxicity through CX3CL1/CX3CR1 signaling

“…The mechanisms underlying divergent effects of CX3CL1 administration to wt and Cx3cl1 -/- mice remain uncertain. In favor of a protective effect of CX3CL1 in cerebral ischemia, Donohue et al (2012) reported that stroke patients exhibited a positive correlation between high plasma CX3CL1 levels and a better clinical outcome. Interestingly, Pimentel-Coelho et al (2013) demonstrated a protective role for CX3CR1 in neonatal hypoxic ischemia in female mice, with a possible gender specific protective effect.…”

The Association of Plasma Fractalkine and Inflammation After Ischemic Stroke

“…Donohue, et al, reported 514 ng/mL (range, 367-650 ng/mL) as the highest plasma fractalkine by 72 hours onset, but patients with more severe strokes had lower concentrations of plasma fractalkine at day 1 and 7 compared to control subjects. (13) We found patients with stroke onset 7-30 days have mean of fractalkine lower than patients with stroke onset <7 days (Figure 2). Other finding on their research, higher fractalkine was associated with a trend toward decreased hsCRP at multiple time points after with stroke onset 7-30 days have higher inflammation than subjects with stroke onset <7 days, and subjects with high inflammation have low fractalkine levels.…”