Relevance of distinct monocyte subsets to clinical course of ischemic stroke patients.
OBJECTIVE
The most common strategy for treating patients with acute ischemic stroke is thrombolytic therapy, though only a few patients receive benefits because of the narrow time window. Inflammation occurring in the central nervous system (CNS) in association with ischemia is caused by immune cells including monocytes and involved in lesion expansion. If the specific roles of monocyte subsets in stroke can be revealed, they may become an effective target for new treatment strategies.


METHODS
We performed immunological examinations of 36 consecutive ischemic stroke patients within 2 days of onset and compared the results with 24 age-matched patients with degenerative disorders. The stroke patients were repeatedly tested for the proportions of monocyte subsets in blood, and serum levels of pro- and anti-inflammatory cytokines immediately after admission, on days 3-7 and 12-16 after stroke onset, and on the day of discharge. In addition, immunological measurements were analyzed for relationships to stroke subtypes and complications, including progressive infarction (PI) and stroke-associated infection (SAI).


RESULTS
Monocyte count was significantly increased from 0-16 days after stroke as compared to the controls (p<0.05). CD14(high)CD16(-) classical and CD14(high)CD16(+) intermediate monocytes were significantly increased from 0-7 and 3-16 days after stroke, respectively (p<0.05), whereas CD14 (dim)CD16(high) non-classical monocytes were decreased from 0-7 days (p<0.05). Cardioembolic infarction was associated with a persistent increase in intermediate monocytes. Furthermore, intermediate monocytes were significantly increased in patients with PI (p<0.05), while non-classical monocytes were decreased in those with SAI (p<0.05). IL-17A levels were positively correlated with monocyte count (r=0.485, p=0.012) as well as the percentage of non-classical monocytes (r=0.423, p=0.028), and negatively with that of classical monocytes (r=-0.51, p=0.007) during days 12-16.


CONCLUSIONS
Our findings suggest that CD14(high)CD16(+) intermediate monocytes have a role in CNS tissue damage during acute and subacute phases in ischemic stroke especially in relation to cardioembolism.
Department of Neurology, Kanazawa Medical University, Uchinada, Ishikawa Prefecture, Japan.
Muichi
M
Kaito
Shin-Ichi
S
Araya
Yuichiro
Y
Gondo
Michiyo
M
Fujita
Naomi
N
Minato
Megumi
M
Nakanishi
Makoto
M
Matsui
D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007239:Infections / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D007249:Inflammation / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D011446:Prospective Studies; D017452:Receptors, IgG / Q000378:metabolism; D020521:Stroke / Q000150:complications / Q000276:immunology / Q000473:pathology*; D013997:Time Factors
D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG