Use of cytokine immunotherapy to block CNS demyelination induced by a recombinant HSV-1 expressing IL-2.
Use of cytokine immunotherapy to block CNS demyelination induced by a recombinant HSV-1 expressing IL-2.
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We previously have described a model of MS in which constitutive expression of murine IL-2 by HSV-1 (HSV-IL-2) causes CNS demyelination in different strains of mice (Zandian et al 2009, IOVS, 50:3275). In the current study, we investigated whether this HSV-IL-2-induced demyelination can be blocked using recombinant viruses expressing different cytokines or by injection of plasmid DNA. We have found that co-infection of HSV-IL-2-infected mice with recombinant viruses expressing IL-12p35, IL-12p40, or IL-12p35 + IL-12p40 did not block the CNS demyelination, and that co-infection with a recombinant virus expressing IFN-γ exacerbated it. In contrast, co-infection with a recombinant virus expressing IL-4 reduced demyelination, while co-infection of HSV-IL-2 infected mice with a recombinant HSV-1 expressing the IL-12 heterodimer (HSV-IL-12p70) blocked the CNS demyelination in a dose-dependent manner. Similarly, injection of IL-12p70 DNA blocked HSV-IL-2-induced CNS demyelination in a dose-dependent manner and injection of IL-35 DNA significantly reduced CNS demyelination. Injection of mice with IL-12p35 DNA, IL-12p40 DNA, IL-12p35 + IL-12p40 DNA, or IL-23 DNA did not have any effect on HSV-IL-2-induced demyelination, while injection of IL-27 DNA increased the severity of the CNS demyelination in the HSV-IL-2 infected mice. This study demonstrates for the first time that IL-12p70 can block HSV-IL-2-induced CNS demyelination and that IL-35 can also reduce this demyelination, whereas IFN-γ and IL-27 exacerbated the demyelination in the CNS of the HSV-IL-2-infected mice. Our results suggest a potential role for IL-12p70 and IL-35 signaling in the inhibition of HSV-IL-2-induced immunopathology by preventing development of autoaggressive T cells.
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影响因子：
4.4
作者：
GALLO, P;PICCINNO, MG;TAVOLATO, B
通讯作者：
TAVOLATO, B
影响因子：
6
作者：
Ghezzi, A;Martinelli, V;Canal, N
通讯作者：
Canal, N
影响因子：
4.4
作者：
Bancroft, AJ;Humphreys, NE;Grencis, RK
通讯作者：
Grencis, RK
DOI：
10.1073/pnas.89.13.6065
发表时间：
1992-07-01
影响因子：
11.1
作者：
HSIEH, CS;HEIMBERGER, AB;MURPHY, KM
通讯作者：
MURPHY, KM
影响因子：
56.9
作者：
Guler, ML;Gorham, JD;Murphy, KM
通讯作者：
Murphy, KM