High IFN-alpha responses associated with depletion of lymphocytes and natural IFN-producing cells during classical swine fever

During the acute phase of the viral hemorrhagic disease, classical swine fever (CSF), a severe hematologic depletion in primary lymphoid organs and depletion of peripheral blood T and B lymphocytes are observed. The onset of these pathologic events is before viremia and independent of leukocyte infection, indicating a host-mediated effect possibly through a cytokine storm. Here, we show that high serum levels of interferon- ¿ (IFN-¿) were found during this phase of CSF, detectable as early as 2 days postinfection and reaching maximum levels 3¿5 days postinfection (250¿1300 U/mL). This IFN-¿ response was related to the virulence of the viral strain used, with avirulent virus not inducing any detectable serum IFN-¿. A progressive depletion of natural IFN-producing cells/plasmacytoid dendritic cells (pDC), the likely in vivo source of IFN-¿, was also induced by the viral infection. An important finding was that the onset of severe lymphopenia was concomitant with the IFN-¿ responses, and all animals with serum IFN-¿ had depleted B and T lymphocytes. A statistically significant correlation between lymphocyte depletion and serum IFN-¿ indicates a relationship between the two events, which is supported by the known hematologic effects of high IFN-¿ doses in vivo