In vivo induction of interleukin-1 (IL-1) production during hemodialysis was investigated by measuring IL-1 activity in monocyte lysates from 59 patients undergoing long-term maintenance hemodialysis with complement activating and non-complement activating devices. In patients dialyzed with new hollow-fiber cuprophane dialyzers, predialytic (T0) monocyte-associated IL-1 activity was 12.5 +/- 3.0 U/ml (mean +/- SEM), a value that was higher than that found in normal individuals (2.85 +/- 0.85 U/ml; P less than 0.0025) and in non-dialyzed patients with chronic renal failure (0.95 +/- 0.85 U/ml, P less than 0.0001). Cell-associated IL-1 activity was consistently increased after five hours of dialysis with cuprophane membranes (42.4 +/- 5.5 U/ml, P less than 0.0005). Systemic complement activation was demonstrated by the finding of increased plasma levels of C3adesArg antigen during dialysis. In patients dialyzed with high permeability polyacrylonitrile and polysulfone membranes, no intradialytic change in cell-associated IL-1 and no complement activation occurred. However, the mean predialytic values of monocyte-associated IL-1 in these patients (that is, 32.9 +/- 5.6 U/ml and 38 +/- 5.65 U/ml for the polyacrylonitrile and the polysulfone groups, respectively) were higher than the predialytic levels of cell-associated IL-1 in the patients from the cuprophane group (P less than 0.0025). Monocytes obtained at the beginning and five hours of dialysis from patients dialyzed with polyacrylonitrile devices, and monocytes obtained at five hours but not at the beginning of dialysis from patients dialyzed with cuprophane membranes, spontaneously released extracellular IL-1 after 24 hours of culture in serum free conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

The generation of compounds such as interleukin 1 (IL-1), tumor necrosis factor alpha (TNFα), and the possible encounter of circulating cells with endotoxin (LPS) have been demonstrated during hemodialysis. All these factors are able to induce the production of IL-6 by human monocytes. Anaphylatoxins can be generated following complement activation by cellulosic membrane dialysis. C5a is known to potentiate the LPS-induced production of IL-1 and TNFα, and we established that recombinant human C5a was able to act synergistically with LPS in the induction of IL-6 by human monocytes. We investigated whether IL-6 could be detected in the serum of long-term hemodialyzed and uremic patients. Using the very sensitive 7TD1 cell line bioassay, we demonstrated that circulating IL-6 activity was present in the serum of all 14 tested patients, whereas it was occasionally present in normal sera. The presence of serum IL-6 was confirmed using an anti-IL-6 antibody and a specific ELISA (109 ± 36 pg/ml). Most patients had a reproducible level of IL-6 activity throughout a period of 10 days. The dialysis session did not significantly modify these levels and patients had similar serum IL-6 activity at the start, during or the at end of the dialysis session. The different parameters of the dialysis session (i.e. standard or filtrated dialyzates, complement-activating or nonactivating membranes) did not significantly influence the levels of IL-6. Elevated levels of IL-6 were also observed in uremic patients compared to normal donors, although significantly lower than in hemodialyzed patients (p = 0.001). Since IL-6 is a hepatocyte-stimulating mediator, we searched for a correlation with C-reactive protein (CRP). Although 4/14 hemodialyzed patients and 5/9 uremic patients had high CRP values, there was no correlation with IL-6 levels. Whether or not the hemodialysis itself or the pathology is responsible of the elevated level of IL-6 is discussed.

A systematic study of the upper cervical spine was performed using magnetic resonance imaging in 25 patients (15 men and 10 women) who had been undergoing hemodialysis for more than 10 years. Seven pseudotumors of the periodontoid soft tissue were disclosed, which were similar to the pannus recently described in rheumatoid arthritis. Bone cystic radiolucencies were observed in association with these pseudotumors in 5 patients. The radiolucencies were located in the atlas (1 in the lateral mass and 1 in the anterior branch) and in the axis (3 in the odontoid process and 1 in the vertebral body). No horizontal or vertical atlantoaxial subluxation was demonstrated. These features were observed only in patients who had amyloid arthropathy. They could be a frequent, yet thus far little-recognized, feature of pZmicroglobulin amyloidosis.Patients with end-stage renal failure who are receiving long-term hemodialysis may develop a variety of osteoarticular abnormalities, which increase in frequency with the duration of dialysis therapy. Many

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