Apoptotic cell-free DNA promotes inflammation in haemodialysis patients

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. We evaluated the occurrence of cfDNA in HD patients and its functional relevance for innate immunity and inflammation. 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. 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.