PRODUCTION OF PROINFLAMMATORY AND REGULATORY MONOKINES IN HEMODIALYSIS-PATIENTS SHOWN AT A SINGLE-CELL LEVEL

Immunologic complications of chronic renal failure are associated with the overproduction of proinflammatory cytokines by monocytes. This is partly due to renal failure itself but is further enhanced by hemodia lysis treatment with frequent contact between blood and dialyzer membr anes. Previous studies have shown an imbalance of proinflammatory and regulatory monokines in these patients. This study examines monokine p roduction in hemodialysis patients using for the first time a very sen sitive method of cytokine detection at a single-cell level by flow cyt ometry (''cytoflow technique''). Monocytes were stained intracellularl y for the production of interleukin-6 (IL-6) and IL-10 after 20 h of c ulture with lipopolysaccharide. It was shown that high levels of proin flammatory IL-6 in hemodialysis patients are due to an increased numbe r of monocytes producing this cytokine, while IL-6 synthesis per cell remains unchanged. In contrast, elevated levels of regulatory IL-IO ar e due to an increased synthesis per cell. This study demonstrates that in healthy subjects there is a population of monocytes producing excl usively LL-IO after 20 h of stimulation by lipopolysaccharide. This di stinct population of regulatory monocytes is infrequent in dialysis pa tients, in whom most of the IL-10-positive monocytes also produce IL-6 . These findings indicate that overproduction of proinflammatory facto rs in dialysis patients is at least in part due to a loss of cytokine- specific differentiation in monocytes.