Background/Purpose: In vitro and in vivo studies suggest that leptin and adiponectin are involved in the development of inflammation in RA patients. Previous findings by our group have shown that levels of these adipokines are significantly higher in RA in comparison with healthy patients, and correlate with variations in DAS28 after two years of follow-up. We have observed that high levels of adiponectin at baseline predict a positive response to DMARD treatment after 6-12 months. However, the biological mechanism of leptin and adiponectin on T cell physiology is still poorly understood. Objetive: To compare the in vitro proliferative and activation effects of leptin and adiponectin on mononuclear (MN) and CD4⁺ T cells from healthy donors and RA patients. Methods: All RA patients included in the present study fulfilled the ACR 2010 criteria and were followed at the rheumatology clinic. Healthy donors samples were obtained from a local blood bank. Mononuclear cells were obtained by Ficoll Paque the same day the blood was obtained. CD4⁺T cells were magnetically purified (Miltengy). In vitro assays were done employing recombinant human leptin and adiponectin (Peprotech). Proliferation was evaluated by MTT technique. Activation was evaluated by flow cytometry (CD25, CD69) and by ELISA (IL-1b, IL-2, IL-6, TNF-a). Th17 differentiation was evaluated by ELISA/cytometry (IL-17A) and western blot (RORyT). Descriptive statistics were employed to evaluate differences between groups and Spearman correlation was used to associate them with clinical parameters. A p-value <0.05 was considered as statistically significant. Results: MN and CD4⁺T cells from RA patients showed a significantly higher proliferative effect when exposed to leptin and adiponectin in comparison with healthy donors. According with these, leptin and adiponectin treatment were able to rescue MN cells from apoptosis induced by etoposide by an IL-2– related mechanism. Interestingly, the level of proliferation correlated with the DAS28 of patients. Similarly, cells from patients were more sensitive to leptin and adiponectin treatment when evaluating CD25⁺/CD69⁺ cell expression and IL-2, TNF-a secretion, in comparison to healthy donor cells. Comparatively, adiponectin treatment was significantly more effective in inducing the expression of CD25, CD69 and IL-6, whereas leptin was a better inductor of IL-2 and TNF-a on RA patient cells. Comparing this with the clinical activity of patients, we only observed a significant correlation between the DAS28 and IL-2 induction when exposed to leptin. On the other hand, CD4⁺T cells from RA patients incubated for several days with leptin induced an increase of IL-6 and IL-17A in the cell culture supernatant and cell expression of RORgT, suggesting a direct mechanism by which high levels of leptin could favor inflammation during the progression of RA. Conclusion: MN and CD4⁺ T cells derived from RA patients were more sensitive to leptin/adiponectin treatment, in comparison to healthy donor cells, with respect to their effects on proliferation, activation and Th17 differentiation. Additionally, clinical activity correlated with the proliferative effect and IL-2 secretion induced by treatment with leptin.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effects-of-leptin-and-adiponectin-on-proliferation-and-activation-were-are-significantly-increased-in-cd4-t-cells-from-rheumatoid-arthritis-patients/