Systematic model of peripheral inflammation after subarachnoid hemorrhage.
OBJECTIVE
To investigate inflammatory processes after aneurysmal subarachnoid hemorrhage (aSAH) with network models.


METHODS
This is a retrospective observational study of serum samples from 45 participants with aSAH analyzed at multiple predetermined time points: <24 hours, 24 to 48 hours, 3 to 5 days, and 6 to 8 days after aSAH. Concentrations of cytokines were measured with a 41-plex human immunoassay kit, and the Pearson correlation coefficients between all possible cytokine pairs were computed. Systematic network models were constructed on the basis of correlations between cytokine pairs for all participants and across injury severity. Trends of individual cytokines and correlations between them were examined simultaneously.


RESULTS
Network models revealed that systematic inflammatory activity peaks at 24 to 48 hours after the bleed. Individual cytokine levels changed significantly over time, exhibiting increasing, decreasing, and peaking trends. Platelet-derived growth factor (PDGF)-AA, PDGF-AB/BB, soluble CD40 ligand, and tumor necrosis factor-α (TNF-α) increased over time. Colony-stimulating factor (CSF) 3, interleukin (IL)-13, and FMS-like tyrosine kinase 3 ligand decreased over time. IL-6, IL-5, and IL-15 peaked and decreased. Some cytokines with insignificant trends show high correlations with other cytokines and vice versa. Many correlated cytokine clusters, including a platelet-derived factor cluster and an endothelial growth factor cluster, were observed at all times. Participants with higher clinical severity at admission had elevated levels of several proinflammatory and anti-inflammatory cytokines, including IL-6, CCL2, CCL11, CSF3, IL-8, IL-10, CX3CL1, and TNF-α, compared to those with lower clinical severity.


CONCLUSIONS
Combining reductionist and systematic techniques may lead to a better understanding of the underlying complexities of the inflammatory reaction after aSAH.
From the University of Texas Health Science Center at Houston.
Jude P J
JPJ
Savarraj
From the University of Texas Health Science Center at Houston.
Kaushik
K
Parsha
From the University of Texas Health Science Center at Houston.
Georgene W
GW
Hergenroeder
From the University of Texas Health Science Center at Houston.
Liang
L
Zhu
From the University of Texas Health Science Center at Houston.
Suhas S
SS
Bajgur
From the University of Texas Health Science Center at Houston.
Sungho
S
Ahn
From the University of Texas Health Science Center at Houston.
Kiwon
K
Lee
From the University of Texas Health Science Center at Houston.
Tiffany
T
Chang
From the University of Texas Health Science Center at Houston.
Dong H
DH
Kim
From the University of Texas Health Science Center at Houston.
Yin
Y
Liu
From the University of Texas Health Science Center at Houston. Huimahn.A.Choi@uth.tmc.edu.
H Alex
HA
Choi
D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005260:Female; D006801:Humans; D007118:Immunoassay; D008297:Male; D008959:Models, Neurological; D015213:Neuroimmunomodulation / Q000502:physiology; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000276:immunology* / Q000628:therapy; D013997:Time Factors
D015415:Biomarkers; D016207:Cytokines