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Leptin and adiponectin, two fat tissue hormones, are increased or tend to be increased in patients with rheumatoid arthritis (RA).1,2 They are likely to be stimulated by proinflammatory cytokines such as tumour necrosis factor (TNF),3,4 and both were found to be increased in the synovial fluid of patients with RA.1,2 Thus, one would expect lowering of serum levels of these two hormones during anti-TNF antibody treatment.
As part of a recently published study with adalimumab (Abbott SpA, Campoverde di Aprilia, Italy),5 we included 32 white patients with RA (30 postmenopausal women, two men) fulfilling the American College of Rheumatology criteria for RA.6 The patients were selected according to the inclusion criteria of the adalimumab Research in Active RA study (ReAct). A total of 16 patients (15 female, one male) did not receive parallel or prior (6 months before) prednisolone treatment. The other 16 patients (15 female, one male) received prednisolone treatment (mean (SEM) 4.6 (0.2) mg/day). The initial mean (SEM) body mass index in the two groups was 22.8 (0.8) kg/m2 (without prednisolone) and 22.3 (0 8) kg/m2 (with prednisolone). We did not see any obvious change of body weight throughout the study. All patients were given additional methotrexate (stable throughout this study) but no other immunosuppressive drugs. Patients were assigned to receive single self-injections of adalimumab subcutaneously at 40 mg every other week. A baseline blood sample was taken 1–2 weeks before the start of adalimumab treatment. Anti-TNF antibodies were infused on weeks 0, 2, 4, 6, 8, 10, and 12. For this study, patients were clinically investigated and blood was drawn between 8 am and 9 am when the patients visited the outpatient clinic on the baseline day and at weeks 2, 6, and 12. The blood was immediately centrifuged and serum was stored at −80°C. The study was approved by the ethics committee of L Sacco University Hospital, Italy.
We used enzyme immunometric assays for the quantitative determination of serum levels of leptin (IBL, Hamburg, Germany), adiponectin (R&D Systems, Wiesbaden, Germany), and interleukin (IL)6 (R&D Systems). Intra-assay and interassay coefficients of variation for all tests were <10%.
Table 1 shows that during 12 weeks of adalimumab treatment in patients, with and without prednisolone, typical measures of inflammation markedly decreased. This indicates that adalimumab was effective in reducing RA associated inflammation. However, serum levels of leptin and adiponectin did not change during adalimumab treatment (fig 1). Interestingly, although having similar body mass indices, patients with prior prednisolone treatment had markedly decreased serum levels of adiponectin in comparison with patients without glucocorticoids (fig 1). This difference remained constant throughout the observation period (fig 1).
In this study, we expected a decrease of serum levels of leptin and adiponectin in patients with RA receiving adalimumab treatment because both hormones are thought to be stimulated by proinflammatory cytokines such as TNF.3,4 We do not believe that an increase of body fat mass has masked a leptin fall because not one anti-TNF treatment study has reported a dramatic effect on body fat mass (even in inflammatory bowel diseases). In addition, others did not find a correlation between serum levels of leptin and disease activity in patients with RA and juvenile arthritis,7,8 which may demonstrate that in these patients the link between inflammation and serum levels of leptin is probably not strong. This finding was later confirmed by another group.9 Others have demonstrated that serum leptin levels are inversely correlated with markers of inflammation such as C reactive protein.10 In our study we did not find any correlation between serum levels of leptin or adiponectin and the number of swollen joints or tender joints, serum IL6, C reactive protein (data not shown, but p values are >0.2). However, adiponectin levels were lower in the patients with RA who had been treated with prednisone; the reason for this is presently unknown.
In conclusion, in patients with RA, serum levels of leptin and adiponectin are not linked to inflammation and are not down regulated by 12 weeks of anti-TNF treatment.
This study was supported by the respective institutions and Abbott SpA., Campoverde di Aprilia, Italy.
Conflict of interest: None.
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