Multiple levels of regulation of the interleukin-6 system in stroke.
Journal - Stroke; a journal of cerebral circulation (United States )
BACKGROUND AND PURPOSE: Serum levels of the cytokine interleukin-6 (IL-6) rise markedly in stroke. IL-6 is a key regulator of inflammatory mechanisms that play an important part in stroke pathophysiology. The action of IL-6 is modified by its soluble receptor subunits sgp130 and sIL-6R. The purpose of this study was to investigate whether serum levels of the receptor subunits are changed after ischemic stroke and to define the role of genetic influences on IL-6 expression in acute stroke. METHODS: In 48 patients with acute stroke and 48 age- and sex-matched control subjects, serum concentrations of IL-6, sgp130, and sIL-6R were measured by enzyme-linked immunosorbent assay. Furthermore, IL-6 promoter haplotypes comprising 4 different polymorphisms (-597G-->A, -572G-->C, -373A(n)T(n), -174G-->C) were determined by DNA sequencing and allele-specific oligonucleotide polymerase chain reaction. The effect of the common haplotypes on IL-6 gene transcription was tested by transfecting reporter fusion genes in the astrocytelike cell line U373. RESULTS: Whereas serum concentrations of IL-6 significantly rose (P<0.001), sgp130 levels were transiently reduced after stroke (P<0.05), and sIL-6R levels remained unchanged. IL-6 levels depended on the infarct size and the haplotype of the promoter region. The common haplotype A-G-8/12-C was associated with low IL-6 levels after stroke and a reduced induction of IL-6 transcription on stimulation with an adenosine analog in vitro. CONCLUSIONS: The data demonstrate genetic variation in the expression of IL-6 in stroke. Induction of the inflammatory response by IL-6 might be enhanced by a transient downregulation of the potential IL-6 antagonist sgp130.
|ISSN : ||1524-4628|
|Mesh Heading : ||Acute Disease Antigens, CD Astrocytes Biological Markers C-Reactive Protein Cell Line Cytokine Receptor gp130 Enzyme-Linked Immunosorbent Assay Female Gene Frequency Genes, Reporter Haplotypes Humans Interleukin-6 Male Membrane Glycoproteins Middle Aged Polymorphism, Genetic Promoter Regions, Genetic Prospective Studies Receptors, Interleukin-6 Stroke Transfection blood cytology metabolism blood analysis blood blood blood blood|
|Mesh Heading Relevant : ||genetics metabolism metabolism|