729
1
Department of Neurology,
2
Department of Microbiology,
4
Department of Epidemiology for Community Health and Medicine, and
5
Department of Radiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
3
Kyoto Industrial Health Association, Multiphasic Health Testing and Service Center, Kyoto, Japan.
Predictive Markers of Blood Cytokine and Chemokine in
Recurrent Brain Infarction
Nagato Kuriyama,
1
Toshiki Mizuno,
1
Masakazu Kita,
2
Yoshinari Nagakane,
1
Akiko Hosomi,
1
Sanae Harada,
3
Kazuo Takeda,
3
Kotaro Ozasa,
4
Kei Yamada,
5
Takahiko Tokuda,
1
Yoshiyuki Watanabe,
4
and Masanori Nakagawa
1
The mechanism of the infammatory response in the vascular wall in atherothrombosis and during the pro-
gression of atherosclerosis has attracted attention. We focused on the potential usefulness of infammatory
markers in chronic recurrent brain infarction, and analyzed the role of infammatory markers in atheroscle-
rosis of the intracranial artery. The subjects were 2 groups of patients treated between 2004 and 2006: a group
of outpatients with recurrent infarction (group RI), who developed atherothrombotic brain infarction twice; an-
other group of outpatients with brain infarction without recurrence (group BI), who developed brain infarction
once and remained free of recurrence for > 1 year; and a group of control subjects with normal brain magnetic
resonance imaging (MRI) and magnetic resonance angiography (MRA) (group C). Plasma samples were col-
lected from each group of patients for the simultaneous measurement of 17 kinds of candidate infammatory
markers, using a fuorescent microbead array system, and the results were compared with head MRA fndings.
The levels of high-sensitivity C-reactive protein (hsCRP) and monocyte chemoattractant protein-1 (MCP-1) were
signifcantly higher in group RI patients than in groups C and BI. Subjects with a hsCRP level ≥0.3 and a MCP-1
level ≥200 in the serum have, respectively, a 1.92 and 2.98 relative risk to have a potential recurrent infarction.
Regarding the relation of infammatory marker levels with MRA fndings, group RI showed signifcantly higher
levels of hsCRP at M1 lesions and MCP-1 at A1 and M1 lesions than group BI ( P < 0.05). In conclusion, the MCP-1
level as well as hsCRP in the blood can be a potential predictive marker of recurrent thrombotic brain infarction,
and may refect infammation that promotes intracranial large-artery atherosclerosis.
Introduction
I
n clinical practice, it is strongly hoped that the second-
ary prevention of brain infarction will reduce the number
of patients with recurrent brain infarction associated with
severe disability. On the other hand, chronic infammation
has been intensively studied in recent years as a mechanism
of atherosclerosis, and it has been shown that vascular endo-
thelial damage and vascular wall infammation are crucial
in atherosclerosis progression and atherothrombosis devel-
opment (Libby 2002; Libby and Ridker 2004). Recent stud-
ies have also reported that infammatory processes play a
signifcant role in the development of cerebral infarction in
an animal model of ischemia/reperfusion-induced brain
infarction, and in patients with brain infarction. However,
much remains to be elucidated regarding the infammatory
aspects in major intracranial arteries (Ross 1993; Ross 1999;
Rost and others 2001).
Although clinical attention has been focused on the
association between high-sensitivity C-reactive protein
(hsCRP) and the progression of intracranial large-artery
atherosclerosis, the expression of various cytokines and
chemokines is involved in hsCRP levels; therefore to eluci-
date the pathogenesis of brain infarction, it is necessary to
further investigate which factors are more directly involved
in the progression of intracranial large-artery atherosclero-
sis (Patel and others 2008).
In this study, we performed extensive mass screening
of cytokines/chemokines, which have been indicated to be
JOURNAL OF INTERFERON & CYTOKINE RESEARCH
Volume 29, Number 11, 2009
© Mary Ann Liebert, Inc.
DOI: 10.1089/jir.2009.0012
RESEARCH REPORT