{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:27:39Z","timestamp":1791217659705,"version":"4.1.0"},"reference-count":28,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,4,7]]},"abstract":"<jats:p>Early infection with murine cytomegalovirus (MCMV) induces circulating levels of interleukin (IL)-12, interferon (IFN)-\u03b3, and tumor necrosis factor (TNF). Studies presented here further characterize these responses by defining kinetics and extending evaluation to include IL-1, IL-6, and glucocorticoids. IL-12 p40, IFN-\u03b3, TNF, IL-1\u03b1, and IL-6 were shown to be increased, but IL-1\u03b2 was undetectable, in serum of MCMV-infected mice. The IL-12 p40, IFN-\u03b3, TNF, and IL-6 responses were dramatic with peak levels reaching &amp;gt;150\u201310,000 pg\/ml at 32\u201340 h after infection and rapidly declining thereafter. Glucocorticoid induction, peaking at 36 h and reaching 30-fold increases above control values, accompanied the cytokine responses. Mice with cytokine deficiencies or neutralized cytokine function demonstrated that IL-6 was the pivotal mediator of the glucocorticoid response, with IL-1 contributing to IL-6 production. The IL-6 requirement appeared to be specific for virus-type stimuli as the synthetic analogue of viral nucleic acid, polyinosinic-polycytidylic acid, also induced IL-6\u2013dependent glucocorticoid release, but treatments with the bacterial product lipopolysaccharide and a non-immune physical restraint stressor elicited IL-6\u2013independent responses. Collectively, the results identify IL-6 as a primary mediator of glucocorticoid induction, and elucidate specific pathways of interactions between immune and neuroendocrine systems during viral infection.<\/jats:p>","DOI":"10.1084\/jem.185.7.1185","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"1185-1192","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":172,"title":["Characterization of Early Cytokine Responses and an Interleukin (IL)-6\u2013dependent Pathway of Endogenous Glucocorticoid Induction during Murine Cytomegalovirus Infection"],"prefix":"10.1084","volume":"185","author":[{"given":"Melanie C.","family":"Ruzek","sequence":"first","affiliation":[{"name":"From the *Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; and \u2021Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Miller","sequence":"additional","affiliation":[{"name":"From the *Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; and \u2021Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Opal","sequence":"additional","affiliation":[{"name":"From the *Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; and \u2021Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley D.","family":"Pearce","sequence":"additional","affiliation":[{"name":"From the *Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; and \u2021Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.","family":"Biron","sequence":"additional","affiliation":[{"name":"From the *Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; and \u2021Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1997,4,7]]},"reference":[{"key":"2023072915280677400_B1","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1084\/jem.180.3.907","article-title":"Interleukin 12, interferon \u03b3, and tumor necrosis factor \u03b1 are the key cytokines of the generalized Shwartzman reaction","volume":"180","author":"Ozmen","year":"1994","journal-title":"J Exp Med"},{"key":"2023072915280677400_B2","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.4049\/jimmunol.148.6.1890","article-title":"Cytokine production after intravenous or peritoneal gram-negative bacterial challenge in mice. 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