{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:39:47Z","timestamp":1791268787283,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2000,10,1]],"date-time":"2000-10-01T00:00:00Z","timestamp":970358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>IL-18 (formerly known as IFN-\u03b3-inducing factor) enhances Th1 responses via effects that are thought to be dependent on and synergistic with IL-12. The potential for IL-18 to exert IL-12-independent effects in delayed-type hypersensitivity (DTH) responses was studied in a model of Th1-directed, DTH-mediated crescentic glomerulonephritis induced by planting an Ag in glomeruli of sensitized mice as well as in cutaneous DTH. Sensitized genetically normal (IL-12+\/+) mice developed proteinuria and crescentic glomerulonephritis with a glomerular influx of DTH effectors (CD4+ T cells, macrophages, and fibrin deposition) in response to the planted glomerular Ag. IL-12p40-deficient (IL-12\u2212\/\u2212) mice showed significant reductions in crescent formation, proteinuria, and glomerular DTH effectors. Administration of IL-18 to IL-12\u2212\/\u2212 mice restored the development of histological (including effectors of DTH) and functional glomerular injury in IL-12\u2212\/\u2212 mice to levels equivalent to those in IL-12+\/+ mice. IL-18 administration to IL-12\u2212\/\u2212 mice increased glomerular ICAM-1 protein expression, but did not restore Ag-stimulated splenocyte IFN-\u03b3, GM-CSF, IL-2, or TNF-\u03b1 production. Sensitized IL-12+\/+ mice also developed cutaneous DTH following intradermal challenge with the nephritogenic Ag. Cutaneous DTH was inhibited in IL-12\u2212\/\u2212 mice, but was restored by administration of IL-18. IL-12+\/+ mice given IL-18 developed augmented injury, with enhanced glomerular and cutaneous DTH, demonstrating the synergistic effects of IL-18 and IL-12 in DTH responses. These studies demonstrate that even in the absence of IL-12, IL-18 can induce in vivo DTH responses and up-regulate ICAM-1 without inducing IFN-\u03b3, GM-CSF, or TNF-\u03b1 production.<\/jats:p>","DOI":"10.4049\/jimmunol.165.8.4649","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:07:54Z","timestamp":1398028074000},"page":"4649-4657","source":"Crossref","is-referenced-by-count":37,"title":["IL-18 Has IL-12-Independent Effects in Delayed-Type Hypersensitivity: Studies in Cell-Mediated Crescentic Glomerulonephritis"],"prefix":"10.1093","volume":"165","author":[{"given":"A Richard","family":"Kitching","sequence":"first","affiliation":[{"name":"Centre for Inflammatory Diseases, Department of Medicine Monash Medical Centre, Monash University , Clayton, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G","family":"Tipping","sequence":"additional","affiliation":[{"name":"Centre for Inflammatory Diseases, Department of Medicine Monash Medical Centre, Monash University , Clayton, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Kurimoto","sequence":"additional","affiliation":[{"name":"Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc. , Fujisaki, Okayama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R","family":"Holdsworth","sequence":"additional","affiliation":[{"name":"Centre for Inflammatory Diseases, Department of Medicine Monash Medical Centre, Monash University , Clayton, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,10,15]]},"reference":[{"key":"2026020213093456700_R1","first-page":"88","volume-title":"Nature","year":"1995"},{"key":"2026020213093456700_R2","first-page":"1541","volume-title":"J. 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