Apoptosis and endotoxins-induced secretion of interleukin-1B and tumor necrosis factor O by mononuclear cells in patients with acute versus chronic renal failure

ABSTRACT

Previous reports suggested a protective effect of chronic renal failure [CRF] against sepsis and endotoxin-induced organ failure and mortality in ARF. The present study was undertaken to investigate apoptosis and endotoxin-induced total production and secretion of interleukin-IB [IL-1B] and secretion of tumor necrosis factor a [TNF alpha] by mononuclear cells in patients with acute versus chronic renal failure. Lipopolysaccharide [LPS] induced IL-1B total production and secretion and TNF alpha secretion by peripheral blood mononuclear cells [PBMC] cultured for 18 hours were determined in patients with advanced CRF but not yet on dialysis [n=13], ARF patients [n=10] and healthy controls [n=10]. In vitro spontaneous apoptosis of cultured PBMC [for 18 hours] was also determined in these subjects. Suppressed secretion of IL-1B [629 +/- 490 pg/ml] by LPS stimulated PBMS was found in patients with CRF compared to patients with ARF [1989 +/- 1209 pg/ml, P<0.05] and healthy controls [1543 +/- 107.3 pg/ml, P<0.05]. A decrease in the total [1346 +/- 998.6 pg/ml] and cell associated [717 +/- 534 pg/ml] LPS induced IL-IB production was also found in them compared to those with ARF [39005 +/- 2516 pg/ml, P<0.05 and 1917 +/- 1308 pg/ml, P<0.05 for total and cell associated levels respectively]. Total production and secretion [absolute value] of LPS induced IL-1B were similar in patients with ARF and healthy controls but with increased cell associated IL-1B production in patients with ARF [P<0.05] LPS-induced TNF alpha secretion by PBMC did not differ significantly in the three groups. Accelerated spontaneous apoptosis of PBMC was found in patients with CRF [30.6 +/- 6.2%] compared to healthy controls [15.8 +/- 9.9%, P<0.05] and to patients with ARF [16.4 +/- 4.7%, P<0.05]. Negative correlation was found between% apoptosis of PBMC and secretion of both LPS induced IL-1B [P<0.01] and TNF alpha [P<0.01] by PBMC in patients with CRF. The reduced capability of PBMC from patients with CRF to secrete adequate amounts of IL-1B in response to LPS together with the accelerated spontaneous apoptosis may be protective mechanisms that decrease the deleterious effect of tissue necrosis and may partly explain the reported fair prognosis of ARF and sepsis in cases with prior CRF