IL-17 synergises with TNF-alpha to induce cartilage destruction in vitro

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Ann Rheum Dis 2002 Oct;61(10):870-6

Interleukin 17 synergises with tumour necrosis factor alpha to induce

cartilage destruction in vitro.

Van Bezooijen RL, Van Der Wee-Pals L, Papapoulos SE, Lowik CW.

Department of Endocrinology and Metabolic Diseases, Leiden University

Medical Centre, PO Box 9600, 2300 RC, Leiden, The Netherlands.

R.L.van_Bezooyen@...

BACKGROUND: Interleukin 17 (IL17) is produced by activated T cells and

has been implicated in the development of bone lesions and cartilage

degradation in rheumatoid arthritis (RA). OBJECTIVE: To determine

whether IL17, alone or together with tumour necrosis factor alpha

(TNFalpha), induces cartilage destruction in vitro. METHODS: Fetal mouse

metatarsals stripped of endogenous osteoclast precursors were used to

study the effect of IL17 on cartilage degradation independently of

osteoclastic resorption. Cartilage destruction was analysed

histologically by Alcian blue staining. RESULTS: IL17 alone, up to 100

ng/ml, had no effect on the cartilage of fetal mouse metatarsals. IL17

(>/=0.1 ng/ml), however, induced severe cartilage degradation when given

together with TNFalpha (>/=1 ng/ml). The cytokine combination decreased

Alcian blue staining, a marker of proteoglycans, throughout the

metatarsals and induced loss of the proliferating and early hypertrophic

chondrocyte zones. TNFalpha alone also decreased Alcian blue staining,

but not as dramatically as the cytokine combination. In addition, it did

not induce loss of chondrocyte zones. Treatment with inhibitors of

matrix metalloproteinase (MMP) activity and nitric oxide synthesis

showed that MMP activity played a part in cartilage degradation, whereas

nitric oxide production did not. CONCLUSIONS: IL17, together with

TNFalpha, induced cartilage degradation in fetal mouse metatarsals in

vitro. IL17 may, therefore, participate in the development of cartilage

destruction associated with RA by enhancing the effects of TNFalpha and

may provide a potential therapeutic target.

PMID: 12228154