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
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Sepsis severityISOIl27 (Mus musculus)126790536; 126790536 RGD 
Sepsis severityIMP 126790536 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il27  (interleukin 27)

Genes (Mus musculus)
Il27  (interleukin 27)

Genes (Homo sapiens)
IL27  (interleukin 27)

Additional Information