PMID- 12562328 OWN - NLM STAT- MEDLINE DCOM- 20030407 LR - 20240413 IS - 0019-2805 (Print) IS - 1365-2567 (Electronic) IS - 0019-2805 (Linking) VI - 108 IP - 2 DP - 2003 Feb TI - Administration of exogenous interleukin-18 and interleukin-12 prevents the induction of oral tolerance. PG - 196-203 AB - Interleukin-18 (IL-18), a pro-inflammatory member of the IL-1 family, has been associated with autoimmunity and allergic disease. This type of pathology is thought to be the result of a defect in immunological tolerance and is often observed in inflammatory disorders of the gut such as coeliac disease, Crohn's disease and ulcerative colitis. IL-18 has been implicated in a number of mucosal immune disorders, where it synergizes with IL-12 to induce the production of interferon-gamma (IFN-gamma). We have therefore investigated the effects of IL-18 and IL-12 administration on the induction of oral tolerance to ovalbumin. The suppression of specific Ig G2a production, delayed-type hypersensitivity responses and IFN-gamma production by antigen-specific T cells were all abrogated by the presence of exogenous IL-12 and IL-18, suggesting that oral tolerance was broken. The expression of the co-stimulatory molecule CD80 on dendritic cells was also shown to be increased by this combination of cytokines. As dendritic cells are thought to be of major importance in the induction of tolerance, this suggests a mechanism by which tolerance to mucosal antigens may be broken in vivo. FAU - Eaton, Alfred D AU - Eaton AD AD - Division of Immunology, Infection & Inflammation, University of Glasgow, Western Infirmary, Glasgow, UK. FAU - Xu, Damo AU - Xu D FAU - Garside, Paul AU - Garside P LA - eng GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Immunoglobulin G) RN - 0 (Interleukin-18) RN - 187348-17-0 (Interleukin-12) RN - 82115-62-6 (Interferon-gamma) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Administration, Oral MH - Animals MH - Cells, Cultured MH - Dendritic Cells/immunology MH - Hypersensitivity, Delayed/immunology MH - Immune Tolerance/*immunology MH - Immunity, Mucosal MH - Immunoglobulin G/biosynthesis MH - Interferon-gamma/biosynthesis MH - Interleukin-12/*immunology MH - Interleukin-18/*immunology MH - Mice MH - Mice, Inbred BALB C MH - Ovalbumin/immunology PMC - PMC1782890 EDAT- 2003/02/04 04:00 MHDA- 2003/04/08 05:00 PMCR- 2004/02/01 CRDT- 2003/02/04 04:00 PHST- 2003/02/04 04:00 [pubmed] PHST- 2003/04/08 05:00 [medline] PHST- 2003/02/04 04:00 [entrez] PHST- 2004/02/01 00:00 [pmc-release] AID - 1570 [pii] AID - 10.1046/j.1365-2567.2003.01570.x [doi] PST - ppublish SO - Immunology. 2003 Feb;108(2):196-203. doi: 10.1046/j.1365-2567.2003.01570.x.