@article{mbs:/content/journal/jgv/10.1099/jgv.0.000665, author = "Nedumpun, Teerawut and Wongyanin, Piya and Sirisereewan, Chaitawat and Ritprajak, Patcharee and Palaga, Tanapat and Thanawongnuwech, Roongroje and Suradhat, Sanipa", title = "Interleukin-1 receptor antagonist: an early immunomodulatory cytokine induced by porcine reproductive and respiratory syndrome virus", journal= "Journal of General Virology", year = "2017", volume = "98", number = "1", pages = "77-88", doi = "https://doi.org/10.1099/jgv.0.000665", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000665", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", keywords = "Interleukin-1 receptor antagonist", keywords = "PRRSV", keywords = "immunomodulatory cytokine", abstract = "Porcine reproductive and respiratory syndrome virus (PRRSV) infection poorly induces pro-inflammatory cytokines (IL-1, IL-6 and TNF-α) and type I IFN production during the early phase of infection. Our microarray analysis indicated strong upregulation of the IL1RA gene in type 2 PRRSV -infected monocyte-derived dendritic cells. Interleukin-1 receptor antagonist (IL-1Ra) is an early inhibitory cytokine that suppresses pro-inflammatory cytokines and T-lymphocyte responses. To investigate the induction of IL-1Ra by PRRSV, monocyte-derived dendritic cells were cultured with type 2 PRRSV or other swine viruses. PRRSV increased both IL1RA gene expression and IL-1Ra protein production in the culture. The enhanced production of IL-1Ra was further confirmed in PRRSV-cultured PBMC and PRRSV-exposed pigs by flow cytometry. Myeloid cell population appeared to be the major IL-1Ra producer both in vitro and in vivo. In contrast to the type 2 PRRSV, the highly pathogenic (HP)- PRRSV did not upregulate IL1RA gene expression in vitro. To determine the kinetics of PRRSV-induced IL1RA gene expression in relation to other pro-inflammatory cytokine genes, PRRSV-negative pigs were vaccinated with a commercially available type 2 modified-live PRRS vaccine or intranasally inoculated with HP-PRRSV. In modified-live PRRS vaccine pigs, upregulation of IL1RA, but not IL1B and IFNA, gene expression was observed from 2 days post- vaccination. Consistent with the in vitro findings, upregulation of IL1RA gene expression was not observed in the HP-PRRSV-infected pigs throughout the experiment. This study identified IL-1Ra as an early immunomodulatory mediator that could be involved in the immunopathogenesis of PRRSV infections.", }