Impairment of innate cellular response to in vitro stimuli in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND

Most crucial in the initial stages of host defence against invading micro-organisms is innate immunity, in which peripheral mononuclear cells, in particular cytokines, are pivotal. Mortality from infections is high in dialysis patients, but it remains unclear if this arises from the ineffectiveness of innate immune mechanisms.

METHODS

In 20 haemodialysis (HD) patients, 20 patients on continuous ambulatory peritoneal dialysis (CAPD), and 15 age-matched controls, we studied cytokine production by monocytes and helper T-cells in response to in vitro stimuli. The most important early-response cytokines for innate immunity, tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta, were tested in monocytes, and interferon-gamma and IL-4 were studied as indicators of polarization of helper T-cells into type 1 and type 2 cells. Peripheral blood cells stimulated with lipopolysaccharide or mitogen were labelled with anti-CD14+ and -CD4+ antibodies and then subjected to intracellular cytokine staining and flow cytometry.

RESULTS

CAPD patients showed significantly reduced synthesis of TNF-alpha and IL-1beta and inhibited T helper phenotype development compared with HD patients and control subjects. In contrast, HD patients showed an unaltered monokine response and a marked polarization of helper T-cells towards the type 1 phenotype. We also found that a single HD treatment potentiated monocytes to synthesize TNF-alpha.

CONCLUSIONS

Circulating immune cells in CAPD patients may be hyporeactive against infections, indicating an unfavourable innate host defence.