High IFN-αResponses Associated with Depletion of Lymphocytes and Natural IFN-Producing Cells During Classical Swine Fever

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Abstract
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- α (IFN-α) 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-α response was related to the virulence of the viral strain used, with avirulent virus not inducing any detectable serum IFN-α. A progressive depletion of natural IFN-producing cells/plasmacytoid dendritic cells (pDC), the likely in vivo source of IFN-α, was also induced by the viral infection. An important finding was that the onset of severe lymphopenia was concomitant with the IFN-α responses, and all animals with serum IFN-α had depleted B and T lymphocytes. A statistically significant correlation between lymphocyte depletion and serum IFN-α indicates a relationship between the two events, which is supported by the known hematologic effects of high IFN-α doses in vivo.