Impaired monocyte cytokine production in critically ill patients with acute renal failure

Abstract

Plasma levels of pro- and anti-inflammatory cytokines are predictive of mortality in patients with acute renal failure (ARF). Anti-inflammatory strategies are postulated to be beneficial in treatment. However, there are few studies simultaneously examining monocyte cytokine production and plasma cytokine levels in patients with ARF. Study populations consisted of 20 critically ill patients with ARF, 19 critically ill patients without ARF (CRIT ILL), 28 healthy subjects (HS), 19 patients with chronic kidney disease (CKD), and 15 patients with end-stage renal disease (ESRD). Monocyte intracellular content of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8, and tumor necrosis factor-alpha (TNF-alpha) was determined by flow cytometry in whole blood. Plasma interleukin 6 and TNF-alpha concentrations were determined by enzyme-linked immunosorbent assay (ELISA). At baseline, there were no differences in intracellular monocyte cytokine levels between groups. After lipopolysaccaride stimulation, monocyte production of IL-1beta, TNF-alpha, and IL-6 in ARF patients was reduced by 41%, 84%, and 45%, respectively, compared to healthy subjects (P < 0.01 in each case), and similarly reduced compared to CKD and ESRD patients, and were similar to CRIT ILL patients. Plasma IL-6 levels were significantly higher in ARF patients than healthy subjects, CKD, and ESRD patients (all P < 0.001). Critically ill patients with acute renal failure have impaired monocyte cytokine production and elevated plasma cytokine levels in a pattern that closely resembles critically ill patients without ARF, and that is dissimilar to CKD and ESRD patients.