title: High IFN-alpha responses associated with depletion of lymphocytes and natural IFN-producing cells during classical swine fever.
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- 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.
authors.affiliation: Institute of Virology and Immunoprophylaxis, Mittelhäusern, Switzerland. artur.summerfield@ivi.admin.ch
authors.forename: A
authors.initials: A
authors.lastname: Summerfield
authors.forename: M
authors.initials: M
authors.lastname: Alves
authors.forename: N
authors.initials: N
authors.lastname: Ruggli
authors.forename: M G M
authors.initials: MG
authors.lastname: de Bruin
authors.forename: K C
authors.initials: KC
authors.lastname: McCullough
mesh_terms: D000818:Animals; D006691:Classical Swine Fever / Q000276:immunology* / Q000821:virology; D006692:Classical Swine Fever Virus / Q000472:pathogenicity*; D003713:Dendritic Cells / Q000276:immunology; D005334:Fever / Q000276:immunology / Q000821:virology; D016898:Interferon-alpha / Q000097:blood* / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D010950:Plasma Cells / Q000276:immunology; D013552:Swine; D014766:Viremia / Q000276:immunology; D014774:Virulence
chemical_list: D016898:Interferon-alpha