RGD Reference Report - Interleukin-30 (IL27p28) alleviates experimental sepsis by modulating cytokine profile in NKT cells. - Rat Genome Database

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Interleukin-30 (IL27p28) alleviates experimental sepsis by modulating cytokine profile in NKT cells.

Authors: Yan, Jun  Mitra, Abhisek  Hu, Jiemiao  Cutrera, Jeffery J  Xia, Xueqing  Doetschman, Thomas  Gagea, Mihai  Mishra, Lopa  Li, Shulin 
Citation: Yan J, etal., J Hepatol. 2016 May;64(5):1128-1136. doi: 10.1016/j.jhep.2015.12.020. Epub 2016 Jan 6.
RGD ID: 126790536
Pubmed: PMID:26767500   (View Abstract at PubMed)
PMCID: PMC4834232   (View Article at PubMed Central)
DOI: DOI:10.1016/j.jhep.2015.12.020   (Journal Full-text)


BACKGROUND & AIMS: Sepsis is an acute systemic inflammatory response to infection associated with high patient mortality (28-40%). We hypothesized that interleukin (IL)-30, a novel cytokine protecting mice against liver injury resulting from inflammation, would generate a protective effect against systemic inflammation and sepsis-induced death.
METHODS: Sepsis was induced by lipopolysaccharide (LPS) or cecal ligation and puncture (CLP). The inhibitory effects of IL-30 on septic inflammation and associated therapeutic effects were determined in wild-type, IL30 (p28)(-/-), IL10(-/-), and CD1d(-/-) mice.
RESULTS: Mice treated with pIL30 gene therapy or recombinant IL-30 protein (rIL30) were protected from LPS-induced septic shock or CLP-induced polymicrobial sepsis and showed markedly less liver damage and lymphocyte apoptosis than control septic mice. The resulting reduction in mortality was mediated through attenuation of the systemic pro-inflammatory response and augmentation of bacterial clearance. Mice lacking IL-30 were more sensitive to LPS-induced sepsis. Natural killer-like T cells (NKT) produced much higher levels of IL-10 and lower levels of interferon-gamma and tumor necrosis factor-alpha in IL-30-treated septic mice than in control septic mice. Likewise, deficiency in IL-10 or NKT cells abolished the protective role of IL-30 against sepsis. Furthermore, IL-30 induced IL-10 production in purified and LPS-stimulated NKT cells. Blocking IL-6R or gp130 inhibited IL-30 mediated IL-10 production.
CONCLUSIONS: IL-30 is important in modulating production of NKT cytokines and subsequent NKT cell-mediated immune regulation of other cells. Therefore, IL-30 has a role in prevention and treatment of sepsis via modulation of cytokine production by NKT.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL27HumanSepsis severityISOIl27 (Mus musculus) RGD 
Il27RatSepsis severityISOIl27 (Mus musculus) RGD 
Il27MouseSepsis severityIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il27  (interleukin 27)

Genes (Mus musculus)
Il27  (interleukin 27)

Genes (Homo sapiens)
IL27  (interleukin 27)


Additional Information