Lars Jørgen Østergaard

Interleukin-37 expression is increased in chronic HIV-1-infected individuals and is associated with inflammation and the size of the total viral reservoir

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Interleukin-37 (IL-37) is a recently identified cytokine with potent anti-inflammatory and immunosuppressive functions. The objective of this study was to compare levels of IL-37 mRNA in immunological subgroups of HIV-1-infected individuals and non-infected controls, to determine IL-37's association with biomarkers of inflammation and reservoir size. This was a cross-sectional study. The HIV-1-infected patients were categorized in three subgroups depending on their cART-treatment status and CD4+ T-cell count. Quantitative RT-PCR was used for the detection of IL-37 mRNA and HIV-1 DNA in PBMCs. Biomarkers in plasma were quantified by ELISA, whereas T-cell activation was determined by flow cytometry. Lastly, lipopolysaccharide (LPS) stimulations of patients PBMCs were carried out to determine differences in IL-37 mRNA response between the subgroups. Sixty HIV-1-infected patients and 20 non-infected controls were included in the study. Steady-state IL-37 mRNA levels in PBMCs were significantly higher in HIV-1-infected individuals compared to non-infected controls: 2.4 fold (p≤0.01) cART-naïve subjects, 3.9 fold (p≤0.0001) Inadequate immunological responders, and 4.0 fold(p≤0.0001) in Immunological responders compared non-infected controls. Additionally, levels of the monocyte inflammatory marker sCD14 correlated with IL-37 mRNA (p=0.03), whereas there was no association with T-cell activation. Finally, we observed a significant correlation between total viral HIV-1 DNA and IL-37 mRNA in PBMCs (p<0.0001). Collectively, our data shows that the level of IL-37 mRNA is affected by chronic HIV-1-infection. A relationship with the activation of the monocyte compartment is suggested by the correlation with sCD14 and interestingly IL-37 could be related to the size of the total viral HIV-1 reservoir.

Original languageEnglish
JournalMolecular Medicine
ISSN1076-1551
DOIs
Publication statusPublished - 14 Apr 2015

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