Characterizing antiviral mechanism of interleukin-32 and a circulating soluble isoform in viral infection

Interleukin-32 (IL-32) is an inflammatory cytokine, and its activity is associated with various auto-inflammatory disorders as well as infectious pathogens such as Mycobacterium tuberculosis, and viral infections. However, the precise antiviral mechanism of IL-32 remains unclear. We assessed the IL-32 level in the sera of H1N1 influenza A patients and IL-32 level was significantly elevated. Next we examined the antiviral activity of recombinant IL-32 gamma (rIL-32 gamma) with WISH cells infected by vesicular stomatitis virus (VSV) but no antiviral activity was observed. Therefore we investigated the supernatant of rIL-32-treated THP-1 cells since this cell line effectively responded to rIL-32 gamma. The supernatant of rIL-32-treated THP-1 cell possessed an antiviral effect and in addition, an agonistic monoclonal antibody further enhanced a specific antiviral activity of rIL-32 gamma. The fractionation and mass spectrometer analysis of the THP-1 cell supernatant revealed that the antiviral activity of rIL-32 gamma is via a THP-1 cell-produced factor, transferrin, rather than the direct effects of rIL-32 gamma on epithelial cells. We also characterized a secreted soluble IL-32 gamma protein in serum of IL-32 gamma transgenic mouse (TG), but not in that of IL-32 alpha TG. The present results suggest that IL-32 gamma expression and its genetic variation in individual could be an important aspect of viral infections. (C) 2012 Elsevier Ltd. All rights reserved.