TRANSCRIPTION, NOT SYNTHESIS, OF INTERLEUKIN-1 AND TUMOR NECROSIS FACTOR BY COMPLEMENT

Stimulation of interleukin-1β (IL-1β) and tumor necrosis factor (TNFα) 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-1β or TNFα 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-1β and TNFα when subsequently stimulated with LPS. Despite the lack of spontaneous monokine synthesis after HD, we observed transcription of mRNA coding for IL-1β and TNFα 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-1β. In the case of TNFα mRNA, Cup induced 26 ± 8% and PS 13 ± 3%. Recombinant C5a induced mRNA for IL-1β in PBMC without detectable IL-1β protein synthesis. We conclude that transcription of mRNA for IL-1β and TNFα during HD is primarily caused by complement activation by Cup, but that LPS or other factors are required for translation of IL-1β and TNFα mRNA transcribed during HD.