IL-1beta, TNF-alpha and IL-6 release from monocytes in haemodialysis patients in relation to dialytic age

Background. It has been suggested that changes in immune response to infectious agents in patients on haemodialysis might be due to impaired monocyte function; uraemic and haemodialysed patients overproduce proinflammatory cytokines, such as interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Methods. We quantitated the cytokines released into the plasma and into the supernatants of 24-h cultured purified monocytes, under basal conditions and after stimulation by lipopolysaccharide from Escherichia coli, in 15 healthy subjects (CON), 20 uraemic patients who had not yet started dialysis (CRF) and 60 haemodialysed patients (HD), who were divided into three groups of 20 patients corresponding to short-, medium- and long-term dialysis. Results. Monocytes from HD patients spontaneously secreted significantly higher levels of cytokines than those from controls and uraemic patients who had not yet started dialysis. After stimulation with lipopolysaccharide (LPS), cytokine levels in culture supernatants of cells from HD patients were significantly lower than those from controls and uraemic patients. Moreover, levels of cytokines in monocyte supernatants and plasma from short-, medium- and long-term haemodialysed patients decreased progressively with dialytic age. Monocytes from haemodialysed patients tended to be constitutively active, but their ability to secrete proinflammatory cytokines was inversely correlated with dialytic age. Conclusions. These results indicate that prolonged treatment with dialysis can be considered a form of chronic stress that causes the progressive activation of monocytes, which ultimately leads to monocyte exhaustion and dysfunction.