{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:10:21Z","timestamp":1790511021236,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T00:00:00Z","timestamp":1156464000000},"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":[[2006,8,25]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Previously, we have demonstrated that macrophages exhibited cytotoxicity toward mouse bladder cancer MBT-2 cells upon bacille Calmette\u2013Gu\u00e9rin (BCG) stimulation. In this study, we have investigated the role of Th1-stimulating cytokines in BCG-induced macrophage cytotoxicity. Thioglycollate-elicited peritoneal exudate cells (PECs) were used as a conventional source for macrophages and the induction of PEC effector functions (cytolytic activity and cytokine production) by BCG was evaluated in vitro. The BCG-activated PECs showed potent cytotoxicity and killed MBT-2 cells in a dose-dependent manner. Depletion of T cells, natural killer (NK) cells, or both, in PEC preparations exhibited a marginal or small reduction of MBT-2 cell killing, suggesting that macrophages played a primary role in PEC cytotoxicity. Transwell assays indicated that the maximal PEC cytotoxicity required both direct cell\u2013cell contact and soluble factors such as interferon (IFN)-\u03b3 and tumour necrosis factor (TNF)-\u03b1. Neutralizing endogenous cytokines interleukin (IL)-12, IL-18, IFN-\u03b3 or TNF-\u03b1 reduced PEC cytotoxicity by 38%, 22%, 15% and 94%, respectively. Supplementation of BCG with recombinant (r)IL-2, rIL-12 or rIL-18 increased PEC cytotoxicity by approximately twofold. Compared with control BCG for PEC stimulation, rBCGs expressing IL-2 or IL-18 showed enhanced MBT-2 cell killing by PECs. Increased cytokine production (IFN-\u03b3, TNF-\u03b1 and IL-6) was also observed in rBCG-stimulated PEC cultures. Taken together, these results suggest that Th1-stimulating cytokines play an important role in BCG-induced macrophage cytotoxicity and that combination of BCG with selected Th1-stimulating cytokines, either supplemented or expressed by BCG, may enhance the effect of BCG in the treatment of bladder cancer patients.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2006.03191.x","type":"journal-article","created":{"date-parts":[[2006,8,31]],"date-time":"2006-08-31T15:08:09Z","timestamp":1157036889000},"page":"181-188","source":"Crossref","is-referenced-by-count":64,"title":["Role of Th1-stimulating cytokines in bacillus Calmette\u2013Gu\u00e9rin (BCG)-induced macrophage cytotoxicity against mouse bladder cancer MBT-2 cells"],"prefix":"10.1093","volume":"146","author":[{"given":"Y","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Urology, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D P","family":"Evanoff","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,8,31]]},"reference":[{"key":"2022010503195234100_b1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0022-5347(17)55282-9","article-title":"Bacillus Calmette\u2013Gu\u00e9rin immunotherapy of superficial bladder cancer","volume":"124","author":"Lamm","year":"1980","journal-title":"J Urol"},{"key":"2022010503195234100_b2","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S1055-3207(18)30447-2","article-title":"Bacillus Calmette\u2013Gu\u00e9rin immunotherapy for superficial bladder cancer. 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