The anti-inflammatory IL-37/SIGIRR axis is functionally compromised in HIV infection

Abstract

IL-37 is a member of the IL-1 family with potent anti-inflammatory effects. Little is known about regulation of the cytokine and of its signaling co-receptor SIGIRR in HIV infection. Our main objective was to investigate how production of the cytokine and expression of SIGIRR on immune cells is regulated in HIV infection. The study was conducted using biological samples from a cross section of HIV-infected individuals. Concentrations of IL-37, TNF-α and soluble form of SIGIRR in serum samples were determined by ELISA. The expression of SIGIRR on immune cells was determined by flow cytometry. IL-37 isoform-specific transcripts were determined in PBMC by RT-PCR using isoform-specific primers. The effects of exogenous IL-37 on HIV replication in human phytohaemagglutinin (PHA) blasts were determined in in-vitro assays. The cytokine concentrations tended to decrease in treatment-naive HIV-infected individuals. They were higher in treated HIV-infected individuals compared with those from treatment-naive ones. Higher concentrations of the cytokine were observed in sera from LTNP. The expression of SIGIRR on immune cells was decreased in HIV-infected individuals. On the other hand, its soluble form increased in the sera in these individuals. The trend was reversed in the patients undergoing antiretroviral treatment. Soluble SIGIRR attenuated anti-inflammatory effects of the cytokine. Serum IL-37 and soluble SIGIRR concentrations correlated with certain clinical parameters of the patients. Furthermore, recombinant human IL-37 inhibited HIV replication in human PHA blasts. The IL-37/SIGIRR axis is functionally compromised in HIV-infected individuals. Targeting the axis may alleviate inflammation and decrease HIV replication in this viral infection.