Malnutrition is an important predictor of mortality in patients on chronic hemodialysis, however the pathogenesis of wasting in this population remains unclear. Experimental data suggest that the dialysis procedure per se leads to enhanced catabolism, as well as direct loss of plasma amino acids and proteins into the dialysate. In the present study, the primary hypothesis examined is that hemodialysis-induced cytokine production is associated with reductions in lean body mass and other plasma markers of nutrition. We used the production of interleukin-1 receptor antagonist (IL-1Ra) by peripheral blood mononuclear cells (PBMC) as an indicator of cytokine production. PBMC were obtained pre-dialysis on the first and second sessions of the week in a cohort of 16 patients on chronic hemodialysis using reprocessed cellulose dialyzers who fulfilled rigorous entry criteria designed to eliminate known etiologies of increased cytokine production, e.g. chronic infections. PBMCs were either immediately frozen (cell content) or incubated for 24 hours at 37 degrees C in the presence or absence of endotoxin 10 ng/ml and total IL-1Ra was measured by radioimmunoassay. Nutritional staus was assessed using body mass index (BMI), total body potassium (TBK), anthropometry-derived arm muscle area (AMA), and measurements of plasma albumin, transferrin, total cholesterol, and triglycerides. Over the subsequent 3 months, patients were monitored carefully for pyrogen reactions, hemodynamic stability and intra-interdialytic symptoms. There was a direct correlation of cell content of IL-1Ra with several indices of nutritional status including BMI (r = 0.90, p = 0.0001), AMA (r = 0. 77, p = 0.0008), serum total cholesterol (r = 0.57, p = 0.03) and serum triglycerides (r = 0. 73, p = 0.002). Endotoxin-stimulated IL-1Ra production correlated directly with AMA (r = 0.59, p = 0.02), TBK (r = 0.71, p = 0.01) and serum triglycerides (r = 0.51, p = 0.05). These studies suggest a direct correlation between nutrition and cytokine production, and that malnutrition could depress cytokine production and potentially contribute to reduced immune responsiveness in patients on chronic hemodialysis.