PMID- 20498200 OWN - NLM STAT- MEDLINE DCOM- 20100727 LR - 20100622 IS - 1468-2060 (Electronic) IS - 0003-4967 (Linking) VI - 69 IP - 7 DP - 2010 Jul TI - Interleukin 6 is not a crucial regulator in an animal model of tumour necrosis factor-mediated bilateral sacroiliitis. PG - 1403-6 LID - 10.1136/ard.2010.129148 [doi] AB - OBJECTIVE: To evaluate the role of interleukin 6 (IL-6) in the pathogenesis of bilateral erosive sacroiliitis in human tumour necrosis factor transgenic (hTNFtg) mice, an animal model of ankylosing spondylitis (AS). METHODS: Histological sections of the sacroiliac joints from hTNFtg and IL-6(-/-)hTNFtg mice were evaluated, and wild type and IL-6(-/-)mice served as controls. mRNA levels of inflammation and tissue degradation related genes isolated from sacroiliac joints were also evaluated by quantitative PCR. RESULTS: Severe, erosive bilateral sacroiliitis in 14-week-old hTNFtg animals was accompanied by an upregulation of mRNAs related to tissue inflammation such as matrix metalloproteinase 3 (MMP3), MMP9 and MMP13 or osteoclast activation such as cathepsin K and tartrate-resistant acid phosphatase. In addition, IL-6 was increased in the sera and in the sacroiliac joints of hTNFtg animals. However, high expression of these marker genes in sacroiliac joints from IL-6(-/-)hTNFtg mice was also found. Moreover, absence of IL-6 in these animals did not alter bilateral, erosive sacroiliitis when compared to hTNFtg littermates. CONCLUSIONS: IL-6 is not a crucial regulator in an animal model of TNF-mediated bilateral, erosive sacroiliitis. This finding questions the potential of IL-6 blockade as a new treatment in patients with AS. FAU - Hayer, Silvia AU - Hayer S AD - Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. FAU - Niederreiter, Birgit AU - Niederreiter B FAU - Nagelreiter, Ionela AU - Nagelreiter I FAU - Smolen, Josef AU - Smolen J FAU - Redlich, Kurt AU - Redlich K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100524 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Animals MH - Arthritis, Experimental/*immunology/pathology MH - Female MH - Gene Expression Regulation/immunology MH - Interleukin-6/deficiency/*immunology MH - Male MH - Matrix Metalloproteinases/metabolism MH - Mice MH - Mice, Transgenic MH - Osteoclasts/metabolism MH - RNA, Messenger/genetics MH - Sacroiliac Joint/*immunology/pathology MH - Tumor Necrosis Factor-alpha/biosynthesis/genetics/*immunology EDAT- 2010/05/26 06:00 MHDA- 2010/07/28 06:00 CRDT- 2010/05/26 06:00 PHST- 2010/05/26 06:00 [entrez] PHST- 2010/05/26 06:00 [pubmed] PHST- 2010/07/28 06:00 [medline] AID - ard.2010.129148 [pii] AID - 10.1136/ard.2010.129148 [doi] PST - ppublish SO - Ann Rheum Dis. 2010 Jul;69(7):1403-6. doi: 10.1136/ard.2010.129148. Epub 2010 May 24.