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

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