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The Journal of Immunology, 1999, 162: 7148-7154.
Copyright © 1999 by The American Association of Immunologists

Therapeutic Protective Effects of IL-12 Combined with Soluble IL-4 Receptor Against Established Infections of Herpes Simplex Virus Type 1 in Thermally Injured Mice1

Hiroyuki Kobayashi*,{dagger}, Makiko Kobayashi*,{dagger}, Tokuichiro Utsunomiya*, David N. Herndon{dagger}, Richard B. Pollard* and Fujio Suzuki2,*,{dagger}

* Department of Internal Medicine, University of Texas Medical Branch, and {dagger} Shriners Burns Hospital, Galveston, TX 77555

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.




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