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Delayed resolution of acute inflammation during zymosan-induced arthritis in leptin-deficient mice

Eiva Bernotiene12, Gaby Palmer1, Dominique Talabot-Ayer1, Ildiko Szalay-Quinodoz3, Michel L Aubert4 and Cem Gabay1*

Author Affiliations

1 Division of Rheumatology, University Hospital and Department of Pathology, University of Geneva School of Medicine, Geneva, Switzerland

2 Department of Immunology, Institute of Experimental and Clinical Medicine at Vilnius University, Vilnius, Lithuania

3 Division of Clinical Pathology, University Hospital, Geneva, Switzerland

4 Division of Development and Growth, Department of Pediatrics, University of Geneva School of Medicine, Geneva, Switzerland

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Arthritis Res Ther 2004, 6:R256-R263  doi:10.1186/ar1174

Published: 26 April 2004


The severity of antigen-induced arthritis (AIA) is decreased in leptin-deficient ob/ob mice. However, joint inflammation in AIA depends on the immune response, which is impaired in ob/ob mice. In the present study we investigated the effects of leptin deficiency on zymosan-induced arthritis (ZIA), which is independent of adaptive immunity. Arthritis was induced by injection of zymosan into the knee joint. Joint swelling was similar after 6 and 24 hours in ob/ob and control mice. However, it remained elevated in ob/ob animals on day 3 whereas values normalized in controls. Histology revealed similar articular lesions in all animals on day 3, but on days 14 and 21 arthritis tended to be more severe in ob/ob mice. The acute phase response, reflected by circulating levels of IL-6 and serum amyloid A, was also more pronounced in ob/ob mice, although corticosterone was significantly elevated in these animals. Similar results were obtained in leptin receptor-deficient db/db mice. Thus, in contrast to AIA, ZIA is not impaired in leptin-deficient animals. On the contrary, resolution of acute inflammation appears to be delayed in the absence of leptin or leptin signalling, suggesting that chronic leptin deficiency interferes with adequate control of the inflammatory response in ZIA.

acute phase response; arthritis; inflammation; interleukin-6; leptin