Human Brain Chemokine and Cytokine Expression in Sepsis: A Report of Three Cases.
BACKGROUND
Sepsis is a systemic response to infection that can affect brain function by inducing resident cells (including astrocytes and microglia) to generate brain chemokines and cytokines. However, there are few studies on the human brain. Since this information may shed further light on pathogenesis, our study objective was to measure the expression of 36 chemokines and cytokines in autopsied brain from 3 cases of sepsis and 10 controls, and to relate this to astrocyte and microglial activation.


METHODS
The right frontal pole was removed at autopsy and chemokine and cytokine expression measured by multiplexed enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (qPCR). Immunohistochemistry and image analysis were carried out to determine the expression of glial fibrillary acidic protein (GFAP), a marker of activated astrocytes, and CD68 and CD45, markers of activated microglial cells.


RESULTS
Concentrations of the chemokines CXCL8, CXCL10, CXCL12, CCL13 and CCL22 were increased in pooled data from the three cases of sepsis (p<0.05); however, their messenger RNA (mRNA) expression was unaltered. CXCL13, CXCL1, CXCL2, CCL1, CCL2, CCL8, CCL20, (interleukin) IL-16, IL-1β and (tumour necrosis factor) TNF concentrations showed increases in two of three sepsis cases. Additionally, individual sepsis cases showed increases in mRNA expression for HDAC (histone deacetylase) 6 and EIF (eukaryotic translation initiation factor) 4A2. Brain GFAP expression was significantly increased (p<0.05) in pooled data from the three sepsis cases. Individual sepsis cases showed increases in CD68 or CD45 expression.


CONCLUSIONS
These expression patterns add to our understanding of the pathogenesis of sepsis and its effects on the brain.
1Department of Pathology,Dalhousie University,Halifax,Nova Scotia,Canada.
Jordan
J
Warford
1Department of Pathology,Dalhousie University,Halifax,Nova Scotia,Canada.
Anna-Claire
AC
Lamport
2Department of Microbiology & Immunology,Dalhousie University,Halifax,Nova Scotia,Canada.
Barry
B
Kennedy
1Department of Pathology,Dalhousie University,Halifax,Nova Scotia,Canada.
Alexander S
AS
Easton
D000368:Aged; D001921:Brain / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D018805:Sepsis / Q000473:pathology*
D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D039601:Eukaryotic Initiation Factor-4A; D006655:Histone Deacetylases
Biomarkers; CNS inflammation; brain injury; infectious diseases; neuroinflammation; sepsis