Interleukin 6 is not a crucial regulator in an animal model of tumour necrosis factor-mediated bilateral sacroiliitis.
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.
Hayer
Silvia
S
Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Niederreiter
Birgit
B
Nagelreiter
Ionela
I
Smolen
Josef
J
Redlich
Kurt
K
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D015850:Interleukin-6 / Q000172:deficiency / Q000276:immunology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012446:Sacroiliac Joint / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases