Transcription, not synthesis, of interleukin-1 and tumor necrosis factor by complement

Abstract

Stimulation of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF alpha) production was studied during in vitro hemodialysis (HD) of whole blood using cuprammonium (Cup) or polysulfone (PS) dialyzers. In the absence of LPS, circulation of whole blood for two hours through Cup or PS dialyzers was not sufficient to induce production of IL-1 beta or TNF alpha in peripheral blood mononuclear cells (PBMC) during subsequent 24 hour culture. However, compared to freshly isolated cells, post-HD PBMC were primed to produce more IL-1 beta and TNF alpha when subsequently stimulated with LPS. Despite the lack of spontaneous monokine synthesis after HD, we observed transcription of mRNA coding for IL-1 beta and TNF alpha after two hours of LPS-free HD. When compared to levels of mRNA induced by 5 ng/ml LPS (100%), Cup induced 27 +/- 6% whereas PS did not induce detectable transcription of IL-1 beta. In the case of TNF alpha mRNA, Cup induced 26 +/- 8% and PS 13 +/- 3%. Recombinant C5a induced mRNA for IL-1 beta in PBMC without detectable IL-1 beta protein synthesis. We conclude that transcription of mRNA for IL-1 beta and TNF alpha during HD is primarily caused by complement activation by Cup, but that LPS or other factors are required for translation of IL-1 beta and TNF alpha mRNA transcribed during HD.

Haemodialysis activates phospholipase A2 enzyme

“…In vitro studies clearly demonstrate that first, cytokine releasing agents cross the membranes from the dialysate to the blood side, second, complement factors induced during blood contact with dialysis membranes in vitro enhance transcription of IL-1 and third, cellulose directly stimulates cytokine production [9,36,37]. Thus in-vitro data clearly support the hypothesis of IL-1 to account for PLA 2 activation.…”

Interleukin-1 Receptor Type I Gene-Deficient Mice Are Less Susceptible toStaphylococcus epidermidisBiomaterial-Associated Infection than Are Wild-Type Mice

“…Kanangat et al (30) reported that high concentrations of lipopolysaccharide, IL-1␤, IL-6, and tumor necrosis factor alpha stimulated intracellular growth in monocytes as well as extracellular growth of Staphylococcus aureus, Pseudomonas aeruginosa, and an Acinetobacter sp., which are all important nosocomial pathogens (30). Observation in humans support a role for increased proinflammation in persistent infection: (i) patients suffering from acute respiratory distress syndrome, caused by acute development of diffuse lung inflammation, have persistently elevated levels of proinflammatory cytokines associated with an increased rate of nosocomial infections (27,40); (ii) patients with long-term exposure to intravascular catheters had exacerbated complications associated with sepsis (37); and (iii) patients who had an extracorporal circulation (11), as well as patients undergoing hemodialysis (28,48), with enhanced levels of circulating proinflammatory cytokines were highly susceptible.…”

Neutrophils: Molecules, Functions and Pathophysiological Aspects

“…It occurs in the early phase of each dialysis session, mainly through the alternative pathway, and closely reflects dialysis membrane biocompatibility, which is observed in dialysis with cellulose membranes such as cuprophan, but not with synthetic membranes, such as polyacrilonitrile (Cheung, 1990). Activated complement-split products, C5a and C3a, were originally ascribed to neutrophil lung sequestration (Arnaout et al, 1985;Hakim et al, 1984), and are now endowed for several indices of dialysis-induced neutrophil and/or monocyte activation, including triggering of protease (Hö rl et al, 1985), reactive oxygen species (ROS) production by neutrophils (DescampsLatscha et al, 1991), and transcription (but not secretion) of the pro-inflammatory cytokines, interleukin-1 (IL-1) and TNF-␣ by monocytes (Schindler et al, 1990). The conjunction of massive generation of ROI in the face of a chronic deficiency of antioxidant systems (Cé ballos-Picot et al, 1996) and of a profound impairment in the balance between pro-inflammatory cytokines and their specific inhibitors (Descamps-Latscha et al, 1995) largely contribute to dialysis-related complications such as an increased rate of atherosclerosis and ␤2-microglobulin amyloidosis arthropathy (Descamps-Latscha, 1993).…”