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A role for leptin in rheumatic diseases?
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  1. G Palmer,
  2. C Gabay
  1. Division of Rheumatology, University Hospital of Geneva and Department of Pathology, University of Geneva School of Medicine, Geneva, Switzerland
  1. Correspondence to:
    Professor C Gabay, Division of Rheumatology, University Hospital of Geneva, 26 avenue Beau-Séjour, 1211 Geneva 14, Switzerland;
    cem.gabay{at}hcuge.ch

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Leptin may influence RA in opposing ways: enhance the expression of Th1 cytokines or limit the inflammatory responses

Leptin is a peptide hormone that has an important role in the regulation of body weight by inhibiting food intake and stimulating energy expenditure. Moreover, leptin exhibits a variety of other effects, including the regulation of endocrine function, reproduction, and immunity.1,2 Consistently, leptin deficient (ob/ob) mice and leptin receptor deficient (db/db) mice are not only severely obese but also display hormonal imbalances, abnormalities in thermoregulation, infertility, and evidence of immune and haematopoietic defects. The role of leptin in the modulation of the immune response and inflammation has lately received particular attention.

LEPTIN AND IMMUNE RESPONSE

It has long been known that ob/ob and db/db mice have an altered immune response.3,4 More recent studies have shown that the long isoform of the leptin receptor (OB-Rb) is expressed in T and B cells and indicated that leptin exerts direct effects on lymphocytes.5–7 Leptin was reported to stimulate the proliferation of T cells in vitro, to promote T helper (Th)1 responses, and to protect T cells from corticosteroid induced apoptosis.5,7

Consistently, ob/ob and db/db mice have a marked reduction in the size and cellularity of the thymus and exhibit defective T cell mediated immunity.3,4 Furthermore, starvation and malnutrition, two conditions characterised by low leptin levels, are also associated with alterations of the immune response and thymic atrophy, which can be reversed by leptin administration.5,7 Despite strong evidence for the direct effects of leptin on T cells in vitro, the connection between leptin deficiency and immune defects in vivo is likely to be more complex. Ob/ob and db/db mice indeed display multiple endocrine and metabolic modifications, including hypercorticosteronaemia and diabetes, which may indirectly affect the immune system. Similarly, …

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