{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:20:31Z","timestamp":1791206431123,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,1,21]]},"abstract":"<jats:p>\n                    Interferon (IFN)-\u03b1\/\u03b2-mediated negative regulation of interleukin 12 (IL-12) and IFN-\u03b3 proteins is reported here. Both IFN-\u03b1 and IFN-\u03b2 inhibited fixed\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    Cowan strain induction of IL-12 and IFN-\u03b3 production by mouse splenic leukocytes in culture. Extended studies with IFN-\u03b1 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-\u03b1\/\u03b2 expressed endogenously during infections with murine cytomegalovirus (MCMV) enhanced early IL-12 and IFN-\u03b3 protein production. Furthermore, during infections of mice with lymphocytic choriomeningitis virus (LCMV), this treatment revealed a previously undetected early IL-12 and IFN-\u03b3 protein expression, and mice deficient in IFN-\u03b1\/\u03b2 receptor function, but not control mice, also expressed endogenous LCMV-induced IL-12. The effects of IFN-\u03b1\/\u03b2 neutralization on production of IL-12 and IFN-\u03b3 during the viral infections were detected in both serum samples and medium conditioned with splenic leukocytes isolated from infected animals.\n                    <jats:italic>In vitro<\/jats:italic>\n                    studies demonstrated that splenic leukocytes isolated from LCMV-infected mice were primed to produce IL-12 in response to stimulation with\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    Cowan strain, but that this responsiveness was sensitive to added IFN-\u03b1. Moreover, endogenous IFN-\u03b1\/\u03b2 induced by LCMV inhibited\n                    <jats:italic>in vivo<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.2.634","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:43:20Z","timestamp":1027680200000},"page":"634-639","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":224,"title":["Interferon-\u03b1\/\u03b2 inhibition of interleukin 12 and interferon-\u03b3 production\n                    <i>in vitro<\/i>\n                    and endogenously during viral infection"],"prefix":"10.1073","volume":"94","author":[{"given":"Leslie\u2009P.","family":"Cousens","sequence":"first","affiliation":[{"name":"Division of Biology and Medicine, Brown University, Providence, RI 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