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.
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.
Katakura
Tatsushi
T
Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Kobayashi
Makiko
M
Fujita
Kazuhiko
K
Herndon
David N
DN
Pollard
Richard B
RB
Suzuki
Fujio
F
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
D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D018664:Interleukin-12