title: A combination therapy using IL-12 and soluble IL-4 receptor on herpes simplex virus Type 1 infection in a human-SCID chimera model of thermal injury.
abstract: Herpes simplex virus type 1 (HSV-1) is a severe pathogen in thermally injured patients. Type 1 T cells are essential for the host's anti-HSV protective immunity. Type 2 cytokines, commonly detected in thermally injured patients, have been described as inhibitors for the type 1 T cell generation. Therefore, the antiviral effects of combination therapy with a type 1 T cell inducer [interleukin (IL)-12] and a type 2 T cell inhibitor [soluble IL-4 receptor (sIL-4R)] were investigated in severe combined immunodeficiency (SCID) mice inoculated with peripheral blood lymphocytes (PBL) of thermally injured patients. Patient PBL-SCID chimeras (SCID mice inoculated with patient PBL) were susceptible to infection with 1 x 10(3) PFU/kg of HSV-1 (0% survival), while healthy PBL-SCID chimeras (SCID mice inoculated with PBL from healthy donors) were resistant (92% survival). When patient PBL-SCID chimeras exposed to HSV-1 were treated with saline, human recombinant (r) IL-12 or human sIL-4R, 0, 0, or 12.5% of them survived, respectively. However, 75% of these chimeras survived when they were treated with rIL-12 and sIL-4R in combination. These results indicate that HSV-1 infection in patient PBL-SCID chimeras was therapeutically controlled by the inducer of type 1 T cell responses and the inhibitor of type 2 T cell responses in combination.
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Katakura
authors.forename: Makiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Fujita
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
authors.forename: Fujio
authors.initials: F
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D002056:Burns / Q000150:complications*; D002678:Chimera; D004359:Drug Therapy, Combination; D006561:Herpes Simplex / Q000150:complications / Q000188:drug therapy*; D018259:Herpesvirus 1, Human; D006801:Humans; D018664:Interleukin-12 / Q000627:therapeutic use*; D008214:Lymphocytes; D008297:Male; D051379:Mice; D016513:Mice, SCID; D019948:Receptors, Interleukin-4 / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013154:Spleen / Q000276:immunology
chemical_list: D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D018664:Interleukin-12