Rheumatology Advance Access originally published online on May 23, 2006
Rheumatology 2006 45(8):944-950; doi:10.1093/rheumatology/kel157
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Towards a pro-inflammatory and immunomodulatory emerging role of leptin
1 Santiago University Clinical Hospital, Research Laboratory 4 (NEIRID LAB, Laboratory of Neuro Endocrine Interactions in Rheumatology and Inflammatory Diseases), Santiago de Compostela, Spain, 2 University of Santiago de Compostela, Department of Physiology, Santiago de Compostela, Spain and 3 Santiago University Clinical Hospital, Research Laboratory 1 (Molecular and Cellular Cardiology), Santiago de Compostela, Spain.
Correspondence to: Oreste Gualillo, PhD PharmD, Santiago University Clinical Hospital, Research Laboratory 4 NEIRID LAB, Research Area, Travesía Choupana sin numero, 15705 Santiago de Compostela, Spain. E-mail: gualillo{at}usc.es
Leptin is a 16 kDa adipocyte-secreted hormone that regulates weight centrally and links nutritional status with neuroendocrine and immune function. Since its cloning in 1994, leptin's role in regulating immune and inflammatory response has become increasingly evident. Actually, the increase of leptin production that occurs during infection and inflammation strongly suggests that leptin is a part of the cytokines loop which governs the inflammatory-immune response and the host defence mechanism. Indeed, leptin stimulates the production of pro-inflammatory cytokines from cultured monocytes and enhances the production of Th1 type cytokines from stimulated lymphocytes. Several studies have implicated leptin in the pathogenesis of autoimmune inflammatory conditions such as type 1 diabetes, rheumatoid arthritis and chronic bowel disease. Obesity is characterized by elevated circulating leptin levels which might contribute significantly to the so called low-grade systemic inflammation, making obese individuals more susceptible to the increased risk of developing cardiovascular diseases, type II diabetes or inflammatory articular degenerative disease such as osteorathritis (OA). As a matter of fact, a key role for leptin in OA has been recently demonstrated since leptin exhibits, in synergy with other pro-inflammatory cytokines, a detrimental effect on articular cartilage cells by promoting nitric oxide synthesis. This review will focus prevalently on the complex relationships existing among leptin, inflammatory response and immunity, trying to provide surprising insights into leptin's role and to discuss challenges and prospects for the future.
*Present address: Beth Israel Deaconess Medical Center, New England Baptist Bone & Joint Institute, Harvard Institutes of Medicine, Boston MA, USA.
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