title: IL-10 immunodepletion from meningococcal sepsis plasma induces extensive changes in gene expression and cytokine release in stimulated human monocytes.
abstract: The severity of systemic meningococcal disease (SMD) correlates to plasma concentrations of LPS and IL-10, with the highest levels detected in non-survivors. Here, plasma from patients with SMD containing high and low concentrations of LPS were incubated with human monocytes before and after immunodepletion of IL-10 to study the effect of IL-10 on gene expression and cytokine release. Patient plasma containing IL-10 induced the expression of 1657 genes in human monocytes when compared with gene expression induced by low LPS plasma. After immunodepletion of IL-10, this number increased to 2260. By directly comparing the gene expression profiles induced before and after immunodepletion of IL-10, the presence of IL-10 differentially regulated 373 genes. Functional classes associated with these genes were cellular function and maintenance, cellular development, cellular growth and proliferation, cell-cell signaling and interaction and cellular movement. Immunodepletion of IL-10 resulted in down-regulation of genes of the leukocyte immunoglobulin-like receptor family, and up-regulation of genes of type I IFN signaling, TLR signaling, the inflammasomes, coagulation and fibrinolysis. Finally, immunodepletion of IL-10 increased the protein levels of IL-1β, IL-8, TNF-α, MIP-1α and MIP-1β. Data suggest that IL-10 in meningococcal sepsis plasma regulates a variety of genes and signaling pathways, likely leading to an overall inhibitory effect on the inflammatory response induced in meningococcal sepsis.
authors.affiliation: Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, Oslo, Norway Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway unni.gnathan@gmail.com.
authors.forename: Unni
authors.initials: U
authors.lastname: Gopinathan
authors.affiliation: Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Berit Sletbakk
authors.initials: BS
authors.lastname: Brusletto
authors.affiliation: Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Ole Kristoffer
authors.initials: OK
authors.lastname: Olstad
authors.affiliation: Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, Oslo, Norway Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Peter
authors.initials: P
authors.lastname: Kierulf
authors.affiliation: Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, Oslo, Norway Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Jens Petter
authors.initials: JP
authors.lastname: Berg
authors.affiliation: Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, Oslo, Norway Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway Department of Pediatrics, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Petter
authors.initials: P
authors.lastname: Brandtzaeg
authors.affiliation: Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Reidun
authors.initials: R
authors.lastname: Øvstebø
mesh_terms: D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005342:Fibrinolysis / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007109:Immunity / Q000235:genetics; D007223:Infant; D058847:Inflammasomes / Q000378:metabolism*; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D008589:Meningococcal Infections / Q000175:diagnosis* / Q000276:immunology; D009345:Neisseria meningitidis / Q000276:immunology*; D018805:Sepsis / Q000175:diagnosis* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D058847:Inflammasomes; D007370:Interferon Type I; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D016753:Interleukin-10
keywords: Interleukin-10; Neisseria meningitidis; gene expression; inflammasomes; leukocyte immunoglobulin-like receptor family; monocytes; septic shock; systemic meningococcal disease; tissue factor; type I interferon signaling