Leptin regulates the immune response to friend and foe

The hormone leptin, primarily produced in fat cells, helps regulate food intake, metabolism and reproduction. It has also been shown to promote and sustain the bodys immune response by binding to T lymphocytes – the frontline cells that protect against infection.

The disease experimental autoimmune encephalomyelitis (EAE) in mice is currently used by researchers as a model of human multiple sclerosis (MS). The disease is characterized by the production of autoreactive T lymphocytes that turn against the body and attack cells within the brain and spinal cord, first inducing weight loss and ultimately resulting in paralysis.

In the January 15 issue of the Journal of Clinical Investigation, Giuseppe Matarese and colleagues at IEOS-CNR at Università di Napoli “Federico II”, Napoli, Italy report that just prior to developing the clinical symptoms of EAE, mice experience a significant burst of leptin which correlates with a reduction in food intake and weight loss. Furthermore, subjecting mice to acute starvation, which prevents the production of leptin, was found to delay the onset and reduce the severity of disease. In addition, leptin secretion from T lymphocytes was found to further contribute to overall leptin production during EAE.

“Once again we witness the remarkable choreography of molecules related to body weight and energy metabolism and the parallel roles of these same molecules in the finely tuned immune response” stated Dr. Lawrence Steinman and colleagues at Stanford University, California in their accompanying commentary. They go on to say that “these results imply that in autoimmunity, stress may be beneficial, and that short-term starvation may help reverse disease”. Stress is detrimental and eating is recommended when fighting bacterial infections, however it appears that in the case of autoimmunity, the opposite holds true – stress and fasting is helpful.

These results suggest that leptin actively contributes to the pathogenesis of EAE, influencing both its onset and clinical severity. Interestingly, leptin is produced at much higher levels in females than males, which may account for the higher susceptibility of females to autoimmune diseases, a fact that has long puzzled scientists. The authors suggest that modulating leptin concentration through dietary approaches, and/or the administration of drugs that interfere with the bodys own production of leptin, may have potential utility in the treatment of MS and other autoimmune diseases.

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CONTACT:
Giuseppe Matarese
Gruppo di ImmunoEndocrinologia
Instituto di Endocrinologia e Oncologia Sperimentale
Consiglio Nazionale delle Richerche (IEOS-CNR) and Cattedra di Immunologia
Dipartmento di Biologia e Patologia Cellulare e Molecolare
Università di Napoli “Federico II”, via S. Pansini 5 – 80131
Napoli
ITALY
Phone: +39-081-7463311
Fax: +39-081-7463252
E-mail: gmatarese@napoli.com

View the PDF of this article at: https://www.the-jci.org/press/16721.pdf

ACCOMPANYING COMMENTARY:
The intricate interplay among body weight, stress, and the immune response to friend or foe

CONTACT:
Lawrence Steinman
Interdepartmental Program in Immunology and the
Department of Neurological Sciences Stanford University
B002 Beckman Center for Molecular medicine
Stanford, CA 94205
USA
Phone: (650) 725-6401
Fax: (650) 725-0627
E-mail: steinman@standford.edu

View the PDF of this commentary at: https://www.the-jci.org/press/17622.pdf