期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1997
卷号：94
期号：2
页码：634-639
DOI：10.1073/pnas.94.2.634
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Interferon (IFN)-/{beta}-mediated negative regulation of interleukin 12 (IL-12) and IFN-{gamma} proteins is reported here. Both IFN- and IFN-{beta} inhibited fixed Staphylococcus aureus Cowan strain induction of IL-12 and IFN-{gamma} production by mouse splenic leukocytes in culture. Extended studies with IFN- demonstrated that inhibition was at the level of biologically active IL-12 p70. Effects were selective, as induction of tumor necrosis factor was unaffected and induction of IL-6 was enhanced. Neutralization of IFN-/{beta} expressed endogenously during infections with murine cytomegalovirus (MCMV) enhanced early IL-12 and IFN-{gamma} protein production. Furthermore, during infections of mice with lymphocytic choriomeningitis virus (LCMV), this treatment revealed a previously undetected early IL-12 and IFN-{gamma} protein expression, and mice deficient in IFN-/{beta} receptor function, but not control mice, also expressed endogenous LCMV-induced IL-12. The effects of IFN-/{beta} neutralization on production of IL-12 and IFN-{gamma} during the viral infections were detected in both serum samples and medium conditioned with splenic leukocytes isolated from infected animals. In vitro studies demonstrated that splenic leukocytes isolated from LCMV-infected mice were primed to produce IL-12 in response to stimulation with Staphylococcus aureus Cowan strain, but that this responsiveness was sensitive to added IFN-. Moreover, endogenous IFN-/{beta} induced by LCMV inhibited in vivo lipopolysaccharide stimulation of IL-12 production. These results demonstrate a new pathway for regulating cytokine responses, and suggest a mechanism for inhibition of IL-12-dependent immune responses during viral infections.
