Interleukin-37 Expression Is Increased in Chronic HIV-1-Infected Individuals and Is Associated with Inflammation and the Size of the Total Viral Reservoir

Højen, Jesper Falkesgaard; Rasmussen, Thomas A; Andersen, Karen Lise Dahl; Winckelmann, Anni; Laursen, Rune R.; Gunst, Jesper Damsgaard; Møller, Holger Jon; Fujita, Mayumi; Østergaard, Lars; Søgaard, Ole Schmeltz; Dinarello, Charles A.; Tolstrup, Martin

doi:10.2119/molmed.2015.00031

Cited by 32 publications

(20 citation statements)

References 60 publications

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“…It is also higher in patients with sputum smear Mtb, and a short-term anti-TB chemotherapy significantly reduce IL-37. Our findings appear to consist with the recent reports indicating that increases in IL-37 expression in infections including HIV-1 and HBV infections are associated with viral loads and inflammation (Anuradha et al, 2015; Hojen et al, 2015; Huang et al, 2015; Li et al, 2013; van de Veerdonk et al, 2014). …”

Section: Discussionsupporting

confidence: 91%

Tuberculosis-sensitized monocytes sustain immune response of interleukin-37

Zhang

Liu

Zheng

et al. 2016

Molecular Immunology

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Roles of human IL-37 in infections remain poorly characterized. Although plasma IL-37 is elevated in patients with tuberculosis (TB), IL-37 source and immune correlate in TB have not been investigated. It is also unknown whether and how TB can influence the ability of immune cells to mount innate responses of IL-37 and pre-inflammatory cytokines. Here, we demonstrated that IL-37b-producing monocytes coincided with a source of elevated plasma IL-37b in TB patients. While IL-37b production in TB was associated with prolonged/complicated TB, TB burdens and inflammatory reactions, it negatively correlated with immune responses of proinflammatory cytokines IL-1β, IL-6 and TNF-α or IL-10. Interestingly, mycobacterial re-infection of monocytes from TB patients, but not healthy BCG-vaccinated controls, enhanced or sustained IL-37b production by cultured monocytes. TB-sensitized monocytes from TB patients mounted more robust immune responses of IL-37b than those of pre-inflammatory cytokines during mycobacterial re-infection in culture. Our data represent new findings in terms of IL-37b responses, immune correlates and potential mechanisms in TB patients.

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Section: Discussionsupporting

confidence: 91%

Tuberculosis-sensitized monocytes sustain immune response of interleukin-37

Zhang

Liu

Zheng

et al. 2016

Molecular Immunology

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“…In a cross sectional study, it was recently shown that the cytokine mRNA was increased more than 2 fold in the PBMC of HIV-infected individuals [115]. The mRNA concentrations correlated with sCD14 (a measure of inflammation), and with viral DNA present in the PBMC but not with T cell activation markers.…”

Section: Role Of Il-37 In the Imbalancementioning

confidence: 98%

Imbalanced production of IL-18 and its antagonist in human diseases, and its implications for HIV-1 infection

et al. 2016

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“…In other diseases, elevated levels of IL‐37 can be interpreted in two ways, either as an appropriate response to limit inflammation, or as a detrimental factor contributing to disease. For example, baseline IL‐37 expression is remarkably higher in PBMCs from HIV‐1‐infected subjects compared to controls, and correlates with the levels of soluble CD14 . These elevated levels of IL‐37 may limit inflammation associated with chronic HIV‐1 infection, or may directly contribute to immunosuppression …”

Section: Role Of Il‐37 In Inflammatory Human Diseasementioning

confidence: 99%

“…For example, baseline IL-37 expression is remarkably higher in PBMCs from HIV-1-infected subjects compared to controls, and correlates with the levels of soluble CD14. 68 These elevated levels of IL-37 may limit inflammation associated with chronic HIV-1 infection, or may directly contribute to immunosuppression. 68 In contrast, lower levels of IL-37 compared to healthy subjects characterize patients with a wide range of inflammatory diseases (Table 1).…”

Section: Role Of Il-3in Inflammatory Human Diseasementioning

confidence: 99%

Suppression of inflammation and acquired immunity by IL‐37

Cavalli

Dinarello

2017

Immunological Reviews

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252

221

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IL-37 is a unique member of the IL-1 family of cytokines, which functions as a natural suppressor of inflammatory and immune responses. Immune and non-immune cells produce IL-37 precursor following pro-inflammatory stimuli. Following activating cleavage by caspase-1, mature IL-37 translocates to the nucleus, where it suppresses transcription of pro-inflammatory genes. Both precursor and mature IL-37 are also secreted in the extracellular space, where they bind IL-18Rα and recruit the IL-1R8 (formerly TIR8 or SIGIRR), which transduces anti-inflammatory signals by suppressing NF-kB and MAPK and by activating Mer-PTEN-DOK pathways. During inflammation, IL-37 restores the metabolism of the cell by reducing succinate, inhibiting mTOR, and activating AMPK. Transgenic mice expressing human IL-37 and wild type mice treated with recombinant human IL-37 are protected from several experimental models of inflammation, including endotoxin shock, colitis, lung and spinal cord injury, coronary artery disease, arthritis and inflammation-induced fatigue, while also exhibiting reduced adaptive immune responses. In humans, IL-37 likely functions to limit excessive inflammation: accordingly, IL-37 levels are abnormal in patients with inflammatory and autoimmune diseases. In this review, we provide an overview of the discovery and biology of IL-37, and discuss the potential for development of this cytokine as a therapeutic agent.

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Interleukin-37 Expression Is Increased in Chronic HIV-1-Infected Individuals and Is Associated with Inflammation and the Size of the Total Viral Reservoir

Cited by 32 publications

References 60 publications

Tuberculosis-sensitized monocytes sustain immune response of interleukin-37

Tuberculosis-sensitized monocytes sustain immune response of interleukin-37

Imbalanced production of IL-18 and its antagonist in human diseases, and its implications for HIV-1 infection

Suppression of inflammation and acquired immunity by IL‐37

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