In vivo intracellular cytokine production by leukocytes during haemodialysis

Several chronic inflammatory changes undergone during chronic haemodialysis are associated with increased pro-inflammatory cytokine production. Although generation of anaphylatoxins has been incriminated in the untoward effects of haemodialysis, it is still debated whether anaphylatoxins stimulate monocyte secretion of TNF-alpha and IL-1. We demonstrate that peripheral mononuclear cells isolated from healthy controls and cultured with complement-activated autologous serum or recombinant C5a induced high levels of IL-1, IL-1ra, IL-8 and MCP-1, low levels of TNFalpha and sTNFRII but no IL-10 and MIP-1alpha. Cytokine production by leukocytes was investigated by FACS analysis in six patients dialysed consecutively with three equivalent low permeability membranes known to activate the complement to different degrees: polysulfone (F6HPS), cellulose acetate (CA) and cuprophane (CP). Percentage of leukocytes expressing IL-1, IL-1ra, TNF-alpha and IL-8 is increased in patients dialysed with CP. Moreover, we show for the first time that haemodialysis is associated with the production of cytokines by circulating neutrophils. Predialysis plasma levels of MCP-1 and TNFRII did not increase during the dialysis session at the time when anaphylatoxin generation was highest. Dialysis with membranes that activate the complement to a high extent induce activation of leukocytes which may explain chronic complications associated with dialysing with CP.