Plasma leptin and neuropeptide Y concentrations in patients with rheumatoid arthritis treated with infliximab, a TNF-α antagonist

Abstract

TNF-α is one of the key proinflammatory cytokines in pathogenesis of rheumatoid arthritis (RA). TNF-α was also found to enhance synthesis of leptin. Leptin is mainly adipocyte-derived hormone controlling appetite and energy expenditure. It acts through inhibition of neuropeptide Y secretion. It is possible that TNF-α-induced leptin secretion contributes to body mass reduction in patients with RA. The study was designed to determine the influence of inactivation of the TNF-α with infliximab on plasma leptin and neuropeptide Y concentrations in patients with RA. Sixteen female patients with RA treated with infliximab and 16 healthy women were investigated. Plasma leptin and neuropeptide Y concentrations were determined before, during and after 1 year management of the patients with infliximab and were compared with body mass index and body fatty and lean mass. There was no difference in plasma leptin concentration between the rheumatoid patients before therapy and the controls (15.6 ± 1.85 and 14.5 ± 2.15 ng/ml, respectively). Neuropeptide Y concentration was higher in the patients than in the controls (54.5 ± 3.96 and 24.8 ± 2.80 pmol/l, respectively). Treatment with infliximab resulted in enhancement in leptin concentration (18.5 ± 2.34 ng/ml) and a slight increase in neuropeptide Y concentration (58.7 ± 4.66 pmol/l). Physiological relationship between leptin and body mass was shown in the patients and was not altered during the treatment. There was no significant correlation between the disease activity and plasma leptin or neuropeptide Y concentrations.

Emerging role of leptin in rheumatoid arthritis

“…They were positively correlated with the BMI and waist circumference Kopec-Medrek et al [20] 2012 n.a. assessed further by a third investigator (Dian Zhou), and a final decision was made by the majority of the votes.…”

“…Targonska-Stepniak et al [95] reported that serum leptin levels were higher in patients with erosive RA. However, some studies have reported that serum leptin levels of RA patients were not different from controls [20,25,33,38], and were concerned significantly with body mass index (BMI) but not disease activity stage (DAS) [33,39]. Anders et al observed that leptin serum levels are not correlated with disease activity in RA patients [40].…”

“…In short, there are several potential explanations for these differing results among these studies: first, the relatively small sample size may not precisely represent the larger patients; secondly, the baseline characteristics such as disease duration, age, race and BMI can be inconsistent, which may affect the expression level of leptin; thirdly, patients with other co-existing autoimmune diseases cannot be excluded from studies, which could be potential confounding factors; and fourthly, different measurement methods of leptin levels, such as radioimmunoassay [20,37,40,100] and enzyme-linked immunosorbent assay (ELISA), may also cause deviation [8,23,30]. In addition, discrepancies in leptin levels in RA patients could be due to different treatments that intervene with the endocrine system, which usually complicates human experimental researches.…”

“…Leptin may have an important role in maintaining energy homeostasis in the anti-inflammatory responses during RA remission [10]. Moreover, treatment for RA with infliximab could cause an increase in plasma leptin levels [20,27]. It has been reported that TNF-α induces the production of preformed leptin from human mature adipocytes and existing differentiated pre-adipocytes [124].…”

Effect of orexin-A (hypocretin-1) on hyperalgesic and cachectic manifestations of experimentally induced rheumatoid arthritis in rats

“…The pathomechanisms for the body mass reduction that occurs in patients with chronic inflammatory diseases remains unclear (Kopec-Medrek et al 2012).…”