Abstract
To investigate the effect of leptin in childhood ITP, we measured plasma leptin in 39 children with acute ITP, after treatment and in remission, and in 33 healthy age/BMI-matched controls. We also cultured ITP and control peripheral blood mononuclear cells (PBMCs) with recombinant leptin to assess its direct effect on pro/anti-inflammatory cytokine gene expression. A significant increase in leptin was observed in children with active disease compared to controls. A significant inverse correlation of leptin with platelet count was also observed in children with acute ITP. Leptin remained high after treatment with IVIg, whereas steroid treatment lowered leptin below control levels. In remission, leptin was in the control range. Cytokine gene expression was significantly increased in children with acute ITP compared with controls, with highest expression for IFN-γ and IL-10. IVIg/steroid treatment significantly decreased IFN-γ and IL-10 expression. In remission, IFN-γ and IL-10 expression remained low. Addition of leptin to PBMCs isolated from patients in remission resulted in a significant increase in IL-10 gene expression compared to controls. Further experiments with purified T-cells and monocytes identified monocytes as the source of leptin-induced IL-10. We suggest that leptin acts as an active anti-inflammatory agent in childhood ITP by promoting IL-10 secretion by monocytes.
Highlights
Leptin has been associated with autoimmunity [39,40] mainly because elevated leptin levels have been observed in rheumatoid arthritis, systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and immune thrombocytopenia (ITP) [25,26,27,28]
Sustained high expression of IFN-γ and resistance to intravenous immunoglobulin (IVIg) treatment have been associated with poor prognosis, whereas a Th2 pattern and IL-10 expression are indicators of stable remission
In agreement with previous studies [26,27,28,45], our results showed an increase in circulating leptin levels in children with acute ITP compared to healthy controls
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. ITP is an autoimmune disease that affects children and adults It is characterized by isolated thrombocytopenia (peripheral platelet count < 100 × 109 /L) in the absence of other causes [29]. Most children with newly diagnosed ITP express the cytokines IL-2 and IFN-γ (with or without IL-4) in vivo, indicating a Th0 pattern or early Th1 cell activation [37]. We investigated the role of leptin in childhood ITP, an autoimmune disease that has clear stages that can be followed closely by platelet counts, and no underlying pathology. To this end, we measured plasma leptin in children with acute ITP, after treatment and in remission, and in healthy controls.
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