Increased levels of IL-10 and IL-1Ra counterbalance the proinflammatory cytokine pattern in acute pediatric immune thrombocytopenia

Goelz, Nadine; Bosch, Alessandra; Rand, Margaret L.; Eekels, Julia J.M.; Franzoso, Francesca; Schmugge, Markus

doi:10.1016/j.cyto.2020.155078

Cited by 17 publications

(16 citation statements)

References 37 publications

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“…Consistent with previous studies [ 34 , 37 , 43 , 49 ], levels of IL-10 and IFN-γ were elevated, whereas IL-4 gene expression was low in newly diagnosed childhood ITP. IL-10 expression was reported to be significantly higher in children with acutely resolving ITP than in those whose disease progressed to chronic.…”

Section: Discussionsupporting

confidence: 91%

“…Childhood ITP does not appear to fully meet the definition of an established autoimmune disease with a polarized type 1 or type 2 response. As previously reported [ 37 , 42 , 43 , 44 ], acute childhood ITP presents with a Th0 or Th1 pattern and, in most cases, low levels of IL-4 and IL-6 that lead to increased expression of HLA-DR molecules on platelet surfaces. Sustained high expression of IFN-γ and resistance to IVIg treatment have been associated with poor prognosis, whereas a Th2 pattern and IL-10 expression are indicators of stable remission.…”

Section: Discussionmentioning

confidence: 53%

“…Therefore, high levels of IL-10 in children with ITP could protect them from an exaggerated inflammatory response and lead them into stable remission. Increased IL-10 gene expression in remission, together with increased IL-4, may counterbalance the pro-inflammatory IFN-γ effect, especially since TGF-β1 levels remain partially suppressed [ 38 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

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The Role of Leptin in Childhood Immune Thrombocytopenia (ITP): An Anti-Inflammatory Agent?

Thomas

Panagoulias

Αγγελετοπούλου

et al. 2021

IJMS

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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.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

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The Role of Leptin in Childhood Immune Thrombocytopenia (ITP): An Anti-Inflammatory Agent?

Thomas

Panagoulias

Αγγελετοπούλου

et al. 2021

IJMS

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“…Another hypothesis for fatigue in ITP is that the destruction of antibody‐coated platelets results in ongoing production of inflammatory cytokines. Although altered cytokine patterns have been found in children with ITP, it remains to be seen whether certain cytokine changes correlate with fatigue 26,27 …”

Section: Discussionmentioning

confidence: 99%

Fatigue in children and adolescents with immune thrombocytopenia

et al. 2020

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Immune thrombocytopenia (ITP), an acquired autoimmune disorder of low platelets and risk of bleeding, has a substantial impact on health-related quality of life (HRQoL). Patients with ITP often report significant fatigue, although the pathophysiology of this is poorly understood. In this observational cohort of 120 children receiving second-line therapies for ITP, we assessed reports of fatigue using the Hockenberry Fatigue Scale. Children and adolescents with ITP reported a similarly high level of fatigue with 54% (29/54) of children and 62% (26/42) of adolescents reporting moderate-to-severe fatigue. There was no correlation between fatigue and age or gender. Adolescents with newly diagnosed and persistent ITP had higher mean fatigue scores than those with chronic ITP (P = 0Á03). Fatigue significantly improved in children and adolescents by 1 month after starting second-line treatments, and this improvement continued to be present at 12 months after starting treatment. Fatigue scores at all time-points correlated with general HRQoL using the Kids ITP Tool, but did not correlate with bleeding symptoms, platelet count, or platelet response to treatment. Fatigue is common in children and adolescents with ITP and may benefit from ITP-directed treatment even in the absence of bleeding symptoms.

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“… 47 , 48 Serum concentrations of IL-10 are elevated in the serum of patients with ITP compared with those in healthy individuals. 32 Furthermore, IL-10 has been reported to affect immunological modulation in ITP 49 , 50 and might, therefore, be involved in the pathophysiology of ITP. 26 , 32 , 38 In this study, however, we observed no significant differences in IL-10 genotypes in ITP patients and healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Effect of Cytokine Gene Polymorphisms on Eltrombopag Reactivity in Japanese Patients with Immune Thrombocytopenia

Nomura

Abe

Yamaoka

et al. 2021

JBM

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Background Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by low platelet counts resulting from antiplatelet autoantibodies. Analysis of polymorphisms in cytokine-encoding genes is important for understanding the pathophysiology of ITP and selecting appropriate treatments. We investigated associations between polymorphisms in cytokine-encoding genes and responses to therapy in Japanese patients with ITP. Methods The participants in this study comprised 153 patients with ITP and 70 healthy controls. We extracted data on sex, age, platelet counts, bleeding symptoms, and therapeutic responses, including those to prednisolone (PSL) and eltrombopag. Genomic DNA was isolated from peripheral blood and polymorphisms in TNF-α, IL-10, TGF-β 1 , and IFN-γ genes were analyzed using the PCR-SSP method. Results Our results showed that the TGF-β 1 +869 C/C genotype might be related to ITP in Japanese patients. The IL-10 −592 C/C and A/A, −819 C/C and T/T, and −1082, −819, −592 ATA/ATA genotypes might be associated with reactivity to PSL. Furthermore, the IL-10 −592 C/A −819 C/T genotypes, IL-10 ACC/ATA genotype, and TGF-β 1 +869 T/T and T/C genotypes might be linked to the response to eltrombopag. Conclusion Our results indicate that analysis of polymorphisms in cytokine-encoding genes could aid in understanding PSL and eltrombopag responsiveness in Japanese patients with ITP.

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Increased levels of IL-10 and IL-1Ra counterbalance the proinflammatory cytokine pattern in acute pediatric immune thrombocytopenia

Cited by 17 publications

References 37 publications

The Role of Leptin in Childhood Immune Thrombocytopenia (ITP): An Anti-Inflammatory Agent?

The Role of Leptin in Childhood Immune Thrombocytopenia (ITP): An Anti-Inflammatory Agent?

Fatigue in children and adolescents with immune thrombocytopenia

Effect of Cytokine Gene Polymorphisms on Eltrombopag Reactivity in Japanese Patients with Immune Thrombocytopenia

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