Therapeutic protective effects of IL-12 combined with soluble IL-4 receptor against established infections of herpes simplex virus type 1 in thermally injured mice.
The effect of combination therapy between IL-12 and soluble IL-4R (sIL-4R) on the established infection of HSV-1 in thermally injured mice (TI mice) was investigated. All of the TI mice infected with lethal amounts of HSV-1 died when IL-12 was given therapeutically at a dose of 500 U/mouse. However, 80% of these mice treated prophylactically with IL-12 survived compared with 0% survival of the same mice treated with saline. The therapeutic administration of IL-12 to TI mice currently infected with HSV-1 caused an 80% survival of these mice when the treatment was combined with sIL-4R. Although IL-12 did not stimulate IFN-gamma production in cultures of splenic T cells from TI mice, IFN-gamma was produced by stimulation with IL-12 when the producer cells were prepared from TI mice that had been treated previously with sIL-4R. After stimulation with anti-CD3 mAb, splenic T cells from TI mice with the established infection of HSV-1 produced IL-4 into their culture fluids. However, IL-4 was not produced by splenic T cells that were prepared from the same infected mice treated with IL-12 and sIL-4R in combination. The results obtained herein indicate that the efficacies of the combination therapy against the established infection of HSV-1 may result from the IFN-gamma production stimulated by IL-12 in TI mice that are treated with sIL-4R for reducing burn-associated type 2 T cell responses.
Kobayashi
H
H
Department of Internal Medicine, University of Texas Medical Branch, Shriners Burns Hospital, Galveston 77555, USA.
Kobayashi
M
M
Utsunomiya
T
T
Herndon
D N
DN
Pollard
R B
RB
Suzuki
F
F
D000818:Animals; D002056:Burns / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D002522:Chlorocebus aethiops; D004359:Drug Therapy, Combination; D006561:Herpes Simplex / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D018259:Herpesvirus 1, Human; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D019948:Receptors, Interleukin-4 / Q000627:therapeutic use*; D012995:Solubility; D013154:Spleen; D013601:T-Lymphocytes / Q000378:metabolism; D014709:Vero Cells
D019948:Receptors, Interleukin-4; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma