We have previously described a model of chronic alcohol ingestion followed by sepsis from cecal ligation and puncture in which alcohol-fed septic mice have higher mortality than water-fed septic mice, associated with altered gut integrity and increased production of TNF and IFNγ by splenic CD4 T cells without alterations in CD8 T cell function.
IFNγ secretion [enzyme-linked immunospot (ELISpot)] in response to stimulation with cytomegalovirus (CMV), pokeweed mitogen (PWM), muromonab-anti-CD3 (OKT3), and human leukocyte antigen (HLA)-DRA-mRNA expression and serum cytokine concentrations were repeatedly [<i>days 1</i>, <i>3</i>, <i>5</i>, and <i>7</i> after intensive care unit (ICU) admission] determined in patients with sepsis (<i>n</i> = 7) and patients undergoing major abdominal surgery (radical prostatectomy, cystectomy, <i>n</i> = 10).
Sepsis was associated with high levels of IL-6, IL-10, G-CSF, and MCP1 and low levels of IFNγ, early sepsis with high levels of IL-6 and G-CSF, severe sepsis with high levels of IL-6 and IL-10, while deaths or sequelae was associated with low levels of IL-4, IL-12, IFNγ, and high levels of GM-CSF.
Guided by clinical and immunological monitoring, adjunctive immunotherapy with IFNγ appears well-tolerated in our cases and improves immune host defense in sepsis induced immuno suppression.
Treatment with Recombinant Interleukin-15 (IL-15) Increases the Number of T Cells and Natural Killer (NK) Cells and Levels of Interferon-γ (IFN-γ) in a Rat Model of Sepsis.
Here, we demonstrate that sunitinib/erlotinib combination achieves sustained suppression of systemic infection at approved dose in DENV-infected IFN-α/β and IFN-γ receptor-deficient mice.
Alternatively, excessive NK cell activation and IFN-γ production can amplify the systemic inflammatory response during sepsis resulting in increased physiological dysfunction and organ injury.
We recruited SIRS (n = 33) and sepsis (n = 89) patients from electronic medical records (EMR) according to whether data on PCT, CRP, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-17, IL-22, TNF-α, and IFN-γ levels were available.
S158A-KI mice were more susceptible to sepsis due to a marked reduction in IL-1β, TNF-α, and IFN-γ production accompanied by an inability to clear bacteria and recruit leukocytes.
Compared with healthy children, children with sepsis demonstrated lower LPS-induced TNF-α production (P < 0.0001) and lower phytohemagglutinin-induced IFN-γ production (P < 0.0001).
Secondary outcome was to assess the following serum cytokine levels: interferon-γ (IFN-γ), interleukin (IL)-10, IL-1β, and tumor necrosis factoralpha (TNFα) at the baseline before LPS injection, 0 hour after LPS injection, and at 2, 4, 24 hours after induction of sepsis (RIC was performed at 2 h after LPS injection).
In this prospective study, Th1/Th2 cytokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, were analyzed in patients with EBV-HLH or sepsis at the onset of disease by flow cytometry.
Natural killer (NK) cells play a crucial role in the pathophysiology of sepsis, leading to exaggerated inflammation due their rapid response and production of pro-inflammatory cytokines such as interferon gamma (IFN-γ).
We demonstrated that spleen-derived IFN-γ induces generation of PD-L1<sup>+</sup>-suppressive neutrophils, implying that the spleen is critically involved in immune suppression during inflammatory diseases such as sepsis.
Interestingly, these data mirrored our observation in septic patients, in which sepsis severity was positively correlated to increased levels of IFN-γ in patients who were serologically positive for <i>T. gondii</i>.
In the sepsis astrocyte models established by co-incubation of LPS and IFN-γ and astrocytes of the cerebral cortex of the rats, the mitochondria with a minor injury in the 6 h group (2.97± 0.92) increased significantly when compared with those in the 0 h group (1.08±0.95), 12 h group (1.70±1.01), and 24 h group (1.59±0.55) (p<0.05); the concentration of adenosine triphosphate (ATP) in the astrocytes of the cerebral cortex of the rats in the 6 h, 12 h, and 24 h groups increased significantly when compared with that in the 0 h group (p<0.05).
Because interferon-gamma (IFN-γ) plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs) that may be associated with sepsis.
Using an in vitro model of endotoxin tolerance (ET), a pivotal feature of sepsis-induced immunosuppression in monocytes, we identified using gene expression profiling by microarray a panel of transcripts associated with the development of ET which expression was restored after immunostimulation with interferon-gamma (IFN-γ).
Whereas more susceptible to systemic infection, IL-1R(-/-) mice depleted of IFN-γ were more resistant to focal inflammation than WT mice similarly depleted of IFN-γ.
IL-7 protein levels were similar in all groups.In cultured PBLs, IFN-γ gene expression was decreased in response to LPS and increased in response to CD3ab with sepsis: IL-7 gene expression increased in response to LPS in controls and to CD3ab with sepsis; Bcl-2 gene expression decreased in response to combined CD3ab and IL-2 with sepsis.
Clinical Pearls and Pitfalls include: (1) A high probability of a defect in the IFN-gamma/IL-12 cascade exists in patients with disseminated or recurrent infection due to poorly pathogenic mycobacteria or systemic infections caused by non-typhi Salmonella species that are persistent and recurrent despite antibiotic therapy.