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

摘要

Background: 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. Objectives: Our main objective was to investigate how production of the cytokine and expression of SIGIRR on immune cells is regulated in HIV infection. Methods: The study was conducted using biological samples from a cross section of HIV-infected individuals. Concentrations of IL-37, TNF-alpha 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. Results: 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. Conclusion: 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.