ENDOTOXINS MODULATE CHRONICALLY TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-6 RELEASE BY UREMIC MONOCYTES

We examined in vivo the release of tumour necrosis factor alpha (TNF a lpha) and interleukin 6 (IL-6) by uraemic monocytes upon stimulation w ith endotoxin-contaminated bicarbonate concentrate. Twelve uraemic pat ients underwent 1-month-subsequent periods of standard haemodialysis ( SHD) with cuprophane (CU), a high-complement-activating membrane (6 pa tients), or haemodiafiltration (HDF) with polyacrylonitrile (PAN), a l ow-complement-activating membrane (6 patients), by using a dialysate p repared with either non-sterile bicarbonate concentrate tanks (phase 1 ) or sterile bicarbonate concentrate bags (phase 2). TNF alpha and IL- 6 concentrations were determined in monocyte supernatants by ELISA; en dotoxin levels in bicarbonate concentrates were measured by a chromoge nic limulus amoebocyte lysate (LAL) assay. A significant increase in L AL reactivity was found in bicarbonate concentrate tanks compared to s terile bags (P<0.001). Non-sterile dialysate caused a significant (P<0 .001) predialytic increase in monocyte TNF alpha release as compared t o controls and non-dialysed uraemic patients. One month treatment with sterile bicarbonate significantly decreased TNF alpha predialytic act ivity in monocyte supernatants (P<0.001) to levels closer to those of non-dialysed uraemic patients. A similar decrease was observed for IL- 6 production. Dialytic treatment induced a further increase in both TN F alpha and IL-6 production, particularly in phase 1. When uraemic pat ients were examined separately according to the different dialytic pro cedures (SHD-CU or HDF-PAN), the use of sterile dialysate (phase 2) ca used a significant decrease of predialysis TNF alpha release in both S HD CU patients (24.1 +/- 8.4 pg/ml versus 55.3 +/- 5.7 pg/ml, P <0.001 ) and HDF PAN-treated patients (16.6 +/- 5.3 pg/ml versus 29.1 +/- 5.4 pg/ml, P<0.005), so that the differences between the dialytic procedu res were completely abolished. In conclusion, TNF alpha and IL-6 relea se may be induced by endotoxin-contaminated dialysate during haemodial ysis. The use of sterile bicarbonate can ameliorate the bioincompatibi lity of CU membranes and probably influences the biocompatibility of P AN membranes. Therefore, regardless of the type of dialyser used, all attempts to obtain an ultrapure dialysate are important to optimize di alytic treatment, in order to attenuate the chronic monocyte activatio n which occurs during haemodialysis.