Stimulation of Interleukin-1 ß Production may be Involved in Unresponsiveness to Erythropoietin Therapy

Recombinant human erythropoietin (rHuEPO) can dramatically improve anemia in dialysis patients, but about 20% of patients show a poor response to this agent. It has been reported that cytokines, including interleukin (IL)-1ß, may inhibit the maturation of erythrocytes. To investigate the mechanisms of unresponsiveness to rHuEPO, we isolated peripheral blood mononuclear cells from 12 patients on continuous ambulatory peritoneal dialysis who were receiving maintenance rHuEPO therapy for renal anemia. Cells were cultured with rHuEPO and IL-1 ß production was assessed. In the six patients who did not respond to rHuEPO therapy, there was a marked increase in IL-1 ß during culture with rHuEPO. In contrast, the addition of rHuEPO to cultures of cells from the six responding patients caused little increase in IL-1 ß, and there was a significant difference between the two groups. Induction of IL-1 ß by rHuEPO may be one cause of persistent anemia in dialysis patients.