Higher plasma fractalkine is associated with better 6-month outcome from ischemic stroke.
OBJECTIVE
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 after 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 after 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.
Departments of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
Megan M
MM
Donohue
Kevin
K
Cain
Dannielle
D
Zierath
Dean
D
Shibata
Patricia M
PM
Tanzi
Kyra J
KJ
Becker
D000368:Aged; D015415:Biomarkers; D002545:Brain Ischemia / Q000097:blood* / Q000628:therapy*; D002097:C-Reactive Protein / Q000032:analysis; D002544:Cerebral Infarction / Q000523:psychology; D054428:Chemokine CX3CL1 / Q000097:blood*; D005260:Female; D023261:Glasgow Outcome Scale; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000097:blood* / Q000628:therapy*; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015415:Biomarkers; D054428:Chemokine CX3CL1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein