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Department of Internal Medicine, University of Texas Medical Branch, and
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-
production in cultures of splenic T cells
from TI mice, IFN-
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-
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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