Related Experiment Video
Updated: Mar 27, 2026
Design of Cecal Ligation and Puncture and Intranasal Infection Dual Model of Sepsis-Induced Immunosuppression
Published on: June 15, 2019
Interleukin-30 (IL27p28) alleviates experimental sepsis by modulating cytokine profile in NKT cells
Jun Yan1, Abhisek Mitra1, Jiemiao Hu1
1Department of Pediatrics Research, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
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.
Insights
Interleukin-30 (IL-30) protects against sepsis-induced death and liver injury by reducing inflammation and enhancing bacterial clearance. This novel cytokine modulates natural killer T cell responses, offering a potential therapeutic strategy for sepsis.
Area of Science:
- Immunology
- Cytokine Biology
- Sepsis Pathophysiology
Background:
- Sepsis is a life-threatening condition characterized by systemic inflammation and high mortality.
- Interleukin-30 (IL-30) is a novel cytokine with known protective effects against inflammatory liver injury.
Purpose of the Study:
- To investigate the protective effects of IL-30 against systemic inflammation and sepsis-induced mortality.
- To elucidate the mechanisms underlying IL-30's therapeutic potential in sepsis.
Main Methods:
- Sepsis was induced using lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in various mouse models.
- The effects of IL-30 gene therapy and recombinant IL-30 protein (rIL30) were assessed.
- Studies included wild-type, IL30(-/-), IL10(-/-), and CD1d(-/-) mice, alongside analysis of natural killer T (NKT) cells and cytokine profiles.
Main Results:
- IL-30 treatment significantly reduced mortality, liver damage, and lymphocyte apoptosis in septic mice.
- IL-30 enhanced bacterial clearance and attenuated the pro-inflammatory response.
- IL-30 induced IL-10 production in NKT cells, which was crucial for its protective effects, while IL-30 deficiency exacerbated sepsis severity.
Conclusions:
- IL-30 plays a critical role in immune regulation by modulating NKT cell cytokine production.
- IL-30 demonstrates potential as a therapeutic agent for preventing and treating sepsis through NKT cell-mediated immune modulation.
