CYTOKINE PRODUCTION AND NUTRITIONAL-STATUS IN HEMODIALYSIS-PATIENTS

Malnutrition is an important predictor of mortality in patients on chr onic hemodialysis, however the pathogenesis of wasting in this populat ion remains unclear. Experimental data suggest that the dialysis proce dure per se leads to enhanced catabolism, as well as direct loss of pl asma 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-l r eceptor antagonist (IL-1Ra) by peripheral blood mononuclear cells (PBM C) as an indicator of cytokine production. PBMC were obtained pre-dial ysis on the first and second sessions of the week in a cohort of 16 pa tients on chronic hemodialysis using reprocessed cellulose dialyzers w ho fulfilled rigorous entry criteria designed to eliminate known etiol ogies of increased cytokine production e.g. chronic infections. PBMCs were either immediately frozen (cell content) or incubated for 24 hour s 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), anth ropometry-derived arm muscle area (AMA), and measurements of plasma al bumin, transferrin, total cholesterol, and triglycerides. Over the sub sequent 3 months, patients were monitored carefully for pyrogen reacti ons 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 = 0.7 7, 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 prod uction correlated directly with AMA (r = 0.59, p = 0.02), TBK (r = 0.7 1, p= 0.01) and serum triglycerides (r = 0.51, p = 0.05). These studie s suggest a direct correlation between nutrition and cytokine producti on, and that malnutrition could depress cytokine production and potent ially contribute to reduced immune responsiveness in patients on chron ic hemodialysis.