EFFECT OF RENAL-FUNCTION ON CYTOKINE SECRETION OF MONOCYTES AND LYMPHOCYTES

The effect of renal function on cytokine secretion capacity of mononuc lear cells was analysed in patients who had not been subjected to any form of renal replacement therapy. The aim of the study was especially to determine whether there is a defect of monocyte function. The pati ents were divided into three groups of 12 on the basis of renal functi on: group I, serum creatinine 1.5-3 mg/dl; group II, 3-6 mg/dl; and gr oup III, > 6 mg/dl. Serving as controls were 36 age- and sex-matched h ealthy volunteers. IL-1beta, IL-6, TNF-alpha, IL-2 and IF-gamma concen trations were measured in the supernatants of stimulated and unstimula ted cells isolated from the blood. Renal function was not found to hav e any effect on the secretion capacity of IL-2 and IF-gamma. However, the secretion capacity of IL-1beta of lipopolysaccharide (LPS)-stimula ted monocytes was reduced in patients of group III to 214 +/- 290 pg/m l, compared with 501 +/- 327 pg/ml in controls (P = 0. 047). The effec t was even more accentuated for IL-6 (group III: 5422 +/- 5116 pg/ml; controls: 16319 +/- 12474 pg/ml; P = 0.019). Spontaneous secretion lev els did not change for any of the cytokines, and LPS-stimulated TNF-al pha secretion was also normal. Highly purified blood monocytes/macroph ages were stained for CD14, HLA-DR, CD11c, and CD4. Neither the percen tage of positive cells nor the fluorescence intensity, as measured by FACS, was influenced by renal function, and no correlation could be es tablished between function and phenotype. The data show clearly a redu ced secretion capacity of IL-1beta and IL-6 in patients with severely impaired renal function.