Regulation of IL-37 and its signaling co-receptor IL-1R8 in HIV infection

Abstract IL-37 is a member of the IL-1 family with potent anti-inflammatory and immune deviating effects. The cytokine exerts its biological effects via IL-1R8 (also formerly known as TIR-8 and SIGIRR), the signaling component of its receptor. Little is known about the regulation of the cytokine and of its receptor in HIV infection. The objective of this study was to investigate how the production of the cytokine and the expression of the signalling component of its receptor on immune cells was regulated in HIV infection. The study was conducted using biological samples from a cross section of HIV-infected individuals. Concentrations of the cytokine and soluble (shed) IL-1R8 in serum samples were determined by ELISA. The expression of IL-1R8 on immune cells was determined by flow cytometry. The effects of exogenous IL-37 on HIV replication in human PHA blasts were determined in in vitro assays. We found that the cytokine concentrations tended to decrease in treatment-naïve HIV-infected individuals compared with the ART-treated patients. Higher concentrations of the cytokine were observed in sera from LTNP. The transcripts for the most complete isoform of the cytokine, b, disappeared from the patients’ PBMC. The expression of IL-1R8 on immune cells was decreased in HIV-infected individuals. On the other hand, concentrations of its soluble form increased in the sera from the virus-infected individuals. The trend was reversed in the patients undergoing anti-retroviral treatment. Soluble IL-1R8 attenuated anti-inflammatory effects of the cytokine. Collectively, these results suggest that the IL-37/IL-1R8 axis is functionally compromised in HIV-infected individuals.