Pro-inflammatory effect of leptin on peripheral blood mononuclear cells of patients with ankylosing spondylitis

Objectives: This study was performed to investigate whether leptin mRNA expression is increased from peripheral blood mononuclear cells (PBMCs) of patients with active ankylosing spondylitis (AS) and whether it stimulates the production of pro-inflammatory cytokines. Methods: Twenty patients with active AS were enrolled and their Bath AS disease activity index (BASDAI) and levels of acute phase reactants were measured. Leptin, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha mRNA expressions and their protein productions were determined in PBMCs of patients with AS using semi-quantitative reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. Then, the results were compared with those from 20 healthy controls, as were clinical and laboratory parameters reflecting disease activity. The changes of pro-inflammatory cytokine productions from PBMCs in response to leptin stimulation were also determined. Results: Leptin, IL-6 and TNF-alpha mRNA expressions of PMBCs from patients with AS were significantly higher than controls. Similar significances were also found in the measurements for leptin and cytokine levels of supernatants, and leptin levels correlated well with IL-6 expression (r = 0.871, p < 0.001) and BASDAI (r = 0.691, p < 0.001) in patients with AS. Stimulation of PBMCs by exogenous leptin significantly increased the production of IL-6 and TNF-alpha. in PBMCs from patients with AS in a dose-dependent fashion and these increases were much exacerbated compared to controls. Conclusion: Our results shows that leptin production is increased and its stimulation of PBMCs significantly increased the production of pro-inflammatory cytokines in patients with active AS, suggesting its pro-inflammatory effect in pathogenesis of AS. (C) 2008 Published by Elsevier Masson SAS.