title: Herpes murine model as a biological assay to test dialyzable leukocyte extracts activity.
abstract: Human dialyzable leukocyte extracts (DLEs) are heterogeneous mixtures of low-molecular-weight peptides that are released on disruption of peripheral blood leukocytes from healthy donors. DLEs improve clinical responses in infections, allergies, cancer, and immunodeficiencies. Transferon is a human DLE that has been registered as a hemoderivate by Mexican health authorities and commercialized nationally. To develop an animal model that could be used routinely as a quality control assay for Transferon, we standardized and validated a murine model of cutaneous HSV-1 infection. Using this model, we evaluated the activity of 27 Transferon batches. All batches improved the survival of HSV-1-infected mice, wherein average survival rose from 20.9% in control mice to 59.6% in Transferon-treated mice. The activity of Transferon correlated with increased serum levels of IFN-γ and reduced IL-6 and TNF-α concentrations. Our results demonstrate that (i) this mouse model of cutaneous herpes can be used to examine the activity of DLEs, such as Transferon; (ii) the assay can be used as a routine test for batch release; (iii) Transferon is produced with high homogeneity between batches; (iv) Transferon does not have direct virucidal, cytoprotective, or antireplicative effects; and (v) the protective effect of Transferon in vivo correlates with changes in serum cytokines.
authors.affiliation: Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, IPN, Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, 11340 México, DF, Mexico.
authors.forename: Nohemí
authors.initials: N
authors.lastname: Salinas-Jazmín
authors.affiliation: Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN, Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, 11340 México, DF, Mexico.
authors.forename: Sergio
authors.initials: S
authors.lastname: Estrada-Parra
authors.affiliation: Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, IPN, Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, 11340 México, DF, Mexico.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Becerril-García
authors.affiliation: Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, IPN, Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, 11340 México, DF, Mexico.
authors.forename: Alberto Yairh
authors.initials: AY
authors.lastname: Limón-Flores
authors.affiliation: Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, IPN, Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, 11340 México, DF, Mexico.
authors.forename: Said
authors.initials: S
authors.lastname: Vázquez-Leyva
authors.affiliation: Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, IPN, Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, 11340 México, DF, Mexico.
authors.forename: Emilio
authors.identifier: 0000-0001-8862-1378
authors.initials: E
authors.lastname: Medina-Rivero
authors.affiliation: Instituto Nacional de Psiquiatría "Ramón De la Fuente Muñiz", Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México, DF, Mexico.
authors.forename: Lenin
authors.initials: L
authors.lastname: Pavón
authors.affiliation: Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 México, DF, Mexico.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Velasco-Velázquez
authors.affiliation: Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, IPN, Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, 11340 México, DF, Mexico ; Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN, Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, 11340 México, DF, Mexico ; Unidad de Investigación Desarrollo e Innovación Médica y Biotecnológica (UDIMEB), Escuela Nacional de Ciencias Biológicas, IPN, Prolongación de Carpio y Plan de Ayala s/n, Col. Sto. Tomás, 11340 México, DF, Mexico.
authors.forename: Sonia Mayra
authors.initials: SM
authors.lastname: Pérez-Tapia
mesh_terms: D000818:Animals; D001681:Biological Assay; D002457:Cell Extracts / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D006561:Herpes Simplex / Q000188:drug therapy* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017193:Skin Diseases, Viral / Q000188:drug therapy* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014709:Vero Cells
chemical_list: D002457:Cell Extracts; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma