Correlation of the L-Arginine Pathway with Thrombo-Inflammation May Contribute to the Outcome of Acute Ischemic Stroke.
BACKGROUND
Immune responses contribute to secondary injury after acute ischemic stroke (AIS), and metabolites of the L-arginine pathway are associated with stroke outcome. Here, we analyzed the relationship of the L-arginine pathway with thrombo-inflammatory biomarkers in AIS and their additive and independent associations to outcome.


METHODS
Serial changes in P-selectin, tPA, MCP-1, sCD40L, IL-6, IL-8, L-arginine, and asymmetric and symmetric dimethylarginine (ADMA, SDMA) were investigated in 55 patients with AIS and without infection within 6 and 72 hours after stroke onset. Outcomes were assessed as National Institutes of Health Stroke Scale (NIHSS) worsening by 24 hours, poststroke infection, and death by 1 month.


RESULTS
Serum levels of L-arginine showed negative correlation, whereas ADMA and SDMA showed positive correlation with thrombo-inflammatory biomarkers in the hyperacute phase. Most of these correlations disappeared by 72 poststroke hours. Correlation of MCP-1 with both ADMA and SDMA levels at 6 hours was associated with both NIHSS worsening and poststroke infections, respectively; sCD40L and SDMA correlation at 6 hours was also associated with NIHSS worsening. Negative correlation between P-selectin and L-arginine concentrations in the hyperacute phase was associated with NIHSS worsening. Strong negative correlation was found between IL-6 and L-arginine levels in the hyperacute phase in patients with poststroke infection. Only L-arginine and SDMA at 72 hours were independently associated with poststroke infection respectively.


CONCLUSIONS
Concentration of L-arginine and ADMA/SDMA differentially correlates with thrombo-inflammation in the hyperacute phase of ischemic stroke. Such correlations are independently associated with poststroke infection but not with other outcomes.
Department of Anaesthesiology and Intensive Care, University of Pecs, Pecs, Hungary. Electronic address: tihamermolnar@yahoo.com.
Tihamer
T
Molnar
Department of Neurology, University of Pecs, Pecs, Hungary.
Gabriella
G
Pusch
Department of Applied Chemistry, University of Debrecen, Debrecen, Hungary.
Lajos
L
Nagy
Department of Applied Chemistry, University of Debrecen, Debrecen, Hungary.
Sandor
S
Keki
Department of Immunology and Biotechnology, University of Pecs, Pecs, Hungary.
Timea
T
Berki
Department of Neurology, University of Pecs, Pecs, Hungary; Department of Neurology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
Zsolt
Z
Illes
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood*; D002545:Brain Ischemia / Q000150:complications; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000502:physiology*; D013223:Statistics as Topic; D020521:Stroke / Q000097:blood* / Q000150:complications* / Q000209:etiology; D013997:Time Factors
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D019007:P-Selectin; C024917:symmetric dimethylarginine; D001120:Arginine
L-arginine; cytokine; dimethylarginine; inflammation; ischemic stroke; outcome