Leptin maturation, and activation levels11. Indeed, LepRs have been

Leptin is one of the most important hormones secreted by adipose
tissue9 and its implication in energetic homeostasis at central level
has been largely described10. Leptin is exerted at the development,
proliferation, anti-apoptotic, maturation, and activation levels11.
Indeed, LepRs have been found in neutrophils, monocytes, and lymphocytes, and
they belong to the family of class I cytokine receptors. The overall leptin
action in the immune system is a pro-inflammatory effect, activating
pro-inflammatory cells, promoting Th1 responses, and mediating the production
of the other pro-inflammatory cytokines, such as TNF-?, IL-2, or IL-6. Leptin
is therefore able to modulate both innate and adaptive immune response.
Moreover, several studies in human revealed that leptin levels associated with
autoimmune disorders, infections and endocrine/metabolic diseases, thus
suggesting a central role of leptin in immune homeostasis and in the
pathogenesis of several inflammatory disorders12.

 Multiple sclerosis (MS) is a chronic, immune-mediated, inflammatory
disorder of the central nervous system (CNS) myelin. The disease is
characterized by autoreactive T-cells that traffic to the brain and the spinal
cord and injury myelin, with the result of chronic or relapsing-remitting paralysis.13Analysis
of the disease susceptibility in naturally leptin-deficient ob/ob mice
before leptin replacement revealed resistance to both active and adoptive
experimental autoimmune encephalomyelitis (EAE) that was reversed by leptin
administration. Leptin replacement converted Th2- to Th1-type response and
shifted IgG antibodies from IgG1 to IgG2a13. In addition, it has
also been recently observed that a serum leptin surge precedes the onset of EAE
in susceptible strains of mice. This peak in serum leptin is correlated with
inflammatory anorexia, weight loss, and development of a pathogenic T-cell
response against myelin14.

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In human MS, it has been reported that secretion of leptin is
increased in serum and cerebrospinal fluid (CSF) of naïve-to-treatment MS
patients and positively correlated with the secretion of interferon (IFN) in
CSF and inversely with the percentage of circulating regulatory T-cells
(TRegs), a key cellular subset in the suppression of immune and autoimmune
responses, involved in the maintenance of T-cell tolerance. In addition, TRegs
in patients with MS were not only inversely related to the leptin levels but
also were reduced in percentage and absolute numbers when compared with healthy
controls. This suggests that the number of TRegs can be affected by leptin secretion13.
The evidence that a significant increase of leptin secretion occurs in the
acute phase of MS and that this event positively correlates with CSF production
of IFN is of particular interest for the pathogenesis and clinical follow-up of
patients with MS. Increased secretion was present in both the serum and CSF of
MS patients and determined loss of correlation between leptin and body mass
index (BMI) 15.