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One potential molecular correlate identified previously was interleukin-6 (IL-6), a cytokine with pleotropic roles in immunity, including influences on T and B cell functions. Given its role as an immune modulator and the correlation with successful anti-LVS vaccination, we examined the role IL-6 plays in the host response to LVS. IL-6-deficient (IL-6 knockout [KO]) mice infected with LVS intradermally or intranasally or anti-IL-6-treated mice, showed greatly reduced 50% lethal doses compared to wild-type (WT) mice. Increased susceptibility was not due to altered splenic immune cell populations during infection or decreased serum antibody production, as IL-6 KO mice had similar compositions of each compared to WT mice. Although LVS-infected IL-6 KO mice produced much less serum amyloid A and haptoglobin (two acute-phase proteins) than WT mice, there were no other obvious pathophysiological differences between LVS-infected WT and IL-6 KO mice. IL-6 KO or WT mice that survived primary LVS infection also survived a high-dose LVS secondary challenge. Using an<jats:italic>in vitro<\/jats:italic>overlay assay that measured T cell activation, cytokine production, and abilities of primed splenocytes to control intracellular LVS growth, we found that IL-6 KO total splenocytes or purified T cells were slightly defective in controlling intracellular LVS growth but were equivalent in cytokine production. Taken together, IL-6 is an integral part of a successful immune response to primary LVS infection, but its exact role in precipitating adaptive immunity remains elusive.<\/jats:p>","DOI":"10.1128\/iai.01249-12","type":"journal-article","created":{"date-parts":[[2012,12,11]],"date-time":"2012-12-11T04:43:06Z","timestamp":1355200986000},"page":"585-597","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Interleukin-6 Is Essential for Primary Resistance to Francisella tularensis Live Vaccine Strain Infection"],"prefix":"10.1128","volume":"81","author":[{"given":"Sherry L.","family":"Kurtz","sequence":"first","affiliation":[{"name":"Laboratory of Mycobacterial Diseases and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oded","family":"Foreman","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Sacramento, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharine M.","family":"Bosio","sequence":"additional","affiliation":[{"name":"Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam R.","family":"Anver","sequence":"additional","affiliation":[{"name":"Pathology\/Histotechnology Laboratory, SAIC\u2014Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Elkins","sequence":"additional","affiliation":[{"name":"Laboratory of Mycobacterial Diseases and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"200","volume-title":"Bergey's manual of systematic bacteriology","author":"Sj\u00f6stedt A","year":"2004","unstructured":"Sj\u00f6stedtA. 2004. 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