BACKGROUND: A proinflammatory environment characterized by the continuous activation of the innate immune system is thought to contribute to the markedly elevated mortality in haemodialysis (HD) patients with end-stage renal disease (ESRD). The presence of circulating cell-free DNA (cfDNA) has been demonstrated as biomarker in many pathologies. METHODS: We evaluated the occurrence of cfDNA in HD patients and its functional relevance for innate immunity and inflammation. RESULTS: Here, we found that cfDNA was enhanced in the plasma of ESRD patients after HD compared to healthy controls. Functionally, cfDNA selectively stimulated the production of the proinflammatory cytokine interleukin (IL)-6 by human monocytes, whereas tumour necrosis factor-α or IL-10 was not induced. Conversely, plasma from HD patients, but not from healthy controls or DNase I-treated HD plasma, induced IL-6 production from monocytes. CONCLUSION: We provide the first evidence that cfDNA has selective immunostimulatory effects on human monocytes. This process may contribute to the proinflammatory milieu observed in HD patients.
BACKGROUND: A proinflammatory environment characterized by the continuous activation of the innate immune system is thought to contribute to the markedly elevated mortality in haemodialysis (HD) patients with end-stage renal disease (ESRD). The presence of circulating cell-free DNA (cfDNA) has been demonstrated as biomarker in many pathologies. METHODS: We evaluated the occurrence of cfDNA in HDpatients and its functional relevance for innate immunity and inflammation. RESULTS: Here, we found that cfDNA was enhanced in the plasma of ESRDpatients after HD compared to healthy controls. Functionally, cfDNA selectively stimulated the production of the proinflammatory cytokine interleukin (IL)-6 by human monocytes, whereas tumour necrosis factor-α or IL-10 was not induced. Conversely, plasma from HDpatients, but not from healthy controls or DNase I-treated HD plasma, induced IL-6 production from monocytes. CONCLUSION: We provide the first evidence that cfDNA has selective immunostimulatory effects on human monocytes. This process may contribute to the proinflammatory milieu observed in HDpatients.
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