Endotoxins modulate chronically tumour necrosis factor alpha and interleukin 6 release by uraemic monocytes.

We examined in vivo the release of tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) by uraemic monocytes upon stimulation with endotoxin-contaminated bicarbonate concentrate. Twelve uraemic patients underwent 1-month-subsequent periods of standard haemodialysis (SHD) with cuprophane (CU), a high-complement-activating membrane (6 patients), or haemodiafiltration (HDF) with polyacrylonitrile (PAN), a low-complement-activating membrane (6 patients), by using a dialysate prepared 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; endotoxin levels in bicarbonate concentrates were measured by a chromogenic limulus amoebocyte lysate (LAL) assay. A significant increase in LAL reactivity was found in bicarbonate concentrate tanks compared to sterile bags (P < 0.001). Non-sterile dialysate caused a significant (P < 0.001) predialytic increase in monocyte TNF alpha release as compared to controls and non-dialysed uraemic patients. One month treatment with sterile bicarbonate significantly decreased TNF alpha predialytic activity 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 TNF alpha and IL-6 production, particularly in phase 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular evidence of organ-related transmission of Kaposi sarcoma-associated herpesvirus or human herpesvirus-8 in transplant patients.

In transplant patients, Kaposi sarcoma (KS)-associated herpesvirus or human herpesvirus-8 (HHV-8) infection is associated with the development of KS, primary effusion lymphoma and Castleman disease. Whether HHV-8 is either reactivated in the recipient or transmitted by the donor has been investigated so far only by serologic studies. Thus, we addressed the issue of HHV-8 transmission in the transplantation setting by molecular methods. We exploited the high level variability of the orf-K1 gene and the polymorphism of the orf-73 gene of the HHV-8 genome to assess the genetic relatedness of the HHV-8 strains identified in the posttransplant KS lesions that developed, simultaneously, 20 months after transplantation, in 2 recipients of twin kidneys from the same cadaver donor. The 100% identity of nucleotide sequence of the most variable viral region and the presence of the same, single orf-73 type in both patients provides strong molecular evidence of organ-related transmission of HHV-8 in the setting of transplantation.