{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:45:02Z","timestamp":1791233102310,"version":"4.1.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2004,6,10]],"date-time":"2004-06-10T00:00:00Z","timestamp":1086825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,6,10]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>Interleukin-18 (IL-18) has been demonstrated to synergize with BCG for induction of a T-helper-type 1 (Th1) immune response. Since successful treatment of superficial bladder cancer with BCG requires proper induction of Th1 immunity, we have developed a recombinant (r) BCG strain that functionally secretes mouse (m) IL-18. This rBCG-mIL-18 strain significantly increased production of the major Th1 cytokine IFN-\u03b3 in splenocyte cultures, at levels comparable to that elicited by control BCG plus exogenous rIL-18. IFN-\u03b3 production by splenocytes was eliminated by addition of neutralizing anti-IL-18 antibody. Endogenous IL-12 played a favourable role whereas IL-10 played an adverse role in rBCG-mIL-18-induced IFN-\u03b3 production. Enhanced host antimycobacterial immunity was observed in mice infected with rBCG-mIL-18 which showed less splenic enlargement and reduced bacterial load compared to control mice infected with BCG. Further, splenocytes from rBCG-mIL-18-infected mice, in response to BCG antigen, displayed increased production of IFN-\u03b3 and GMCSF, decreased production of IL-10, elevated cellular proliferation and higher differentiation of IFN-\u03b3-secreting cells. rBCG-mIL-18 also enhanced BCG-induced macrophage cytotoxicity against bladder cancer MBT-2 cells in a dose-dependent manner. Neutralizing all endogenous macrophage-derived cytokines tested (IL-12, IL-18 and TNF-\u03b1) as well as IFN-\u03b3 severely diminished the rBCG-mIL-18-induced macrophage cytolytic activity, indicating a critical role for these cytokines in this process. Cytokine analysis for supernatants of macrophage-BCG mixture cultures manifested higher levels of IFN-\u03b3 and TNF-\u03b1 in rBCG-mIL-18 cultures than in control BCG cultures. Taken together, this rBCG-mIL-18 strain augments BCG's immunostimulatory property and may serve as a better agent for bladder cancer immunotherapy and antimycobacterial immunization.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2004.02522.x","type":"journal-article","created":{"date-parts":[[2004,6,15]],"date-time":"2004-06-15T19:24:39Z","timestamp":1087327479000},"page":"24-34","source":"Crossref","is-referenced-by-count":65,"title":["Recombinant<i>Mycobacterium bovis<\/i>bacillus Calmette-Gu\u00e9rin (BCG) expressing mouse IL-18 augments Th1 immunity and macrophage cytotoxicity"],"prefix":"10.1093","volume":"137","author":[{"given":"Y","family":"LUO","sequence":"first","affiliation":[{"name":"Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"YAMADA","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"CHEN","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A A","family":"RYAN","sequence":"additional","affiliation":[{"name":"Mycobacterial Research Laboratory, Centenary Institute of Cancer Medicine and Cell Biology, Newtown, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D P","family":"EVANOFF","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J A","family":"TRICCAS","sequence":"additional","affiliation":[{"name":"Mycobacterial Research Laboratory, Centenary Institute of Cancer Medicine and Cell Biology, Newtown, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"O'DONNELL","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,6,10]]},"reference":[{"key":"2022011223190692200_b1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0022-5347(17)55282-9","article-title":"Bacillus Calmette-Gu\u00e9rin immunotherapy of superficial bladder cancer","volume":"124","author":"Lamm","year":"1980","journal-title":"J Urol"},{"key":"2022011223190692200_b2","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1016\/S0140-6736(98)07422-4","article-title":"BCG immunotherapy of bladder cancer: 20 years on","volume":"353","author":"Alexandroff","year":"1999","journal-title":"Lancet"},{"key":"2022011223190692200_b3","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S1055-3207(18)30447-2","article-title":"Bacillus Calmette-Gu\u00e9rin immunotherapy for superficial bladder cancer. 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