{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:58:28Z","timestamp":1781769508792,"version":"3.54.5"},"reference-count":36,"publisher":"Hindawi Limited","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p>Bacille Calmette-Gu\u00e9rin (BCG) vaccine exerts nonspecific immunostimulatory effects and may therefore represent a novel therapeutic option to treat sepsis-induced immunoparalysis. We investigated whether BCG vaccination modulates the systemic innate immune response in humans<jats:italic>in vivo<\/jats:italic>during experimental endotoxemia. We used inactivated gamma-irradiated BCG vaccine because of the potential risk of disseminated disease with the live vaccine in immunoparalyzed patients. In a randomized double-blind placebo-controlled study, healthy male volunteers were vaccinated with gamma-irradiated BCG (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>n<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>10<\/mml:mn><\/mml:math>) or placebo (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mi>n<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>10<\/mml:mn><\/mml:math>) and received 1\u2009ng\/kg lipopolysaccharide (LPS) intravenously on day 5 after vaccination to assess the<jats:italic>in vivo<\/jats:italic>immune response. Peripheral blood mononuclear cells were stimulated with various related and unrelated pathogens 5, 8 to 10, and 25 to 35 days after vaccination to assess<jats:italic>ex vivo<\/jats:italic>immune responses. BCG vaccination resulted in a scar in 90% of vaccinated subjects. LPS administration elicited a profound systemic immune response, characterized by increased levels of pro- and anti-inflammatory cytokines, hemodynamic changes, and flu-like symptoms. However, BCG modulated neither this<jats:italic>in vivo<\/jats:italic>immune response, nor<jats:italic>ex vivo<\/jats:italic>leukocyte responses at any time point. In conclusion, gamma-irradiated BCG is unlikely to represent an effective treatment option to restore immunocompetence in patients with sepsis-induced immunoparalysis. This trial is registered with<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT02085590\">NCT02085590<\/jats:ext-link>.<\/jats:p>","DOI":"10.1155\/2015\/261864","type":"journal-article","created":{"date-parts":[[2015,3,27]],"date-time":"2015-03-27T18:01:32Z","timestamp":1427479292000},"page":"1-11","source":"Crossref","is-referenced-by-count":11,"title":["Gamma-Irradiated Bacille Calmette-Gu\u00e9rin Vaccination Does Not Modulate the Innate Immune Response during Experimental Human Endotoxemia in Adult Males"],"prefix":"10.1155","volume":"2015","author":[{"given":"Linda A. C.","family":"Hamers","sequence":"first","affiliation":[{"name":"Department of Intensive Care Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands"},{"name":"Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthijs","family":"Kox","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob J. W.","family":"Arts","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastiaan","family":"Blok","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenneke","family":"Leentjens","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands"},{"name":"Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Pickkers","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. 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