Enhancement of in-Vitro Human Interleukin-1 Production by Sodium Acetate

Bingel, Marion; Koch, Karl-M.; Lonnemann, Gerhard; Dinarello, C. A.; Shaldon, Stanley

doi:10.1016/s0140-6736(87)90703-3

Cited by 138 publications

(52 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The influence of the dialysis membrane was also reported in so far as patients treated solely with AN69 less frequently show signs of Aß2M than those treated with a cellulosic membrane [7,8]. Also, the role of the dialysate was stressed, as the presence of acetate and/or endotoxin induced ß2M production [9,10].…”

Section: Discussionmentioning

confidence: 91%

Remarkable Removal of Beta-2-Microglobulin by On-Line Hemodiafiltration

et al. 1998

View full text Add to dashboard Cite

Eight chronic, anuric hemodialysis patients were randomly treated with a high-flux polysulphone dialyzer (F80), using 6 different modes: conventional bicarbonate hemodialysis (HD), hemodiafiltration (HDF) with a replacement solution at 40, 60, 80 or 100 ml/min in postdilution and 80 ml/min in predilution. The differences in β₂-microglobulin (β2M) reduction ratio and clearance were evaluated statistically by analysis of variance (ANOVA). Both studies revealed no significant difference between HD and HDF40 in postdilution, but an increasing significant difference from HDF60 to HDF100 in postdilution and with HDF80 in predilution. The mean reduction ratio ranged from 49.7 (HD) to 72.7% (HDF 100 ml/min), showing an overall statistically significant difference (p = 0.0000). For the clearance, the range was between 63.8 (HD) and 116.8 ml/min (HDF 100 ml/min) (p = 0.0000). β2M in the effluent dialysate with HDF100 ml/min reached up to a mean of 258 mg/session. Concerning small molecules (BUN, creatinine and P), there was a statistically significant different clearance for creatinine and especially for P with HDF 100 ml/min. Conclusion: HDF with an on-line replacement solution at 100 ml/min and a high-flux and biocompatible polysulphone membrane represents a new tool for enhanced removal of β2M. Besides a significant increase in creatinine and especially in phosphorus clearance is noted.

show abstract

Section: Discussionmentioning

confidence: 91%

Remarkable Removal of Beta-2-Microglobulin by On-Line Hemodiafiltration

et al. 1998

View full text Add to dashboard Cite

show abstract

“…At this osmolarity, there was as much IL-8 induced as that induced by IL-la or LPS, two well-established stimulators of IL-8 gene expression and synthesis (19). The stimulatory effect of these (20).…”

Section: Discussionmentioning

confidence: 91%

Osmotic regulation of cytokine synthesis in vitro.

Shapiro

Dinarello

1995

Proc. Natl. Acad. Sci. U.S.A.

243

137

View full text Add to dashboard Cite

These studies were undertaken to investigate the therapeutic mechanism of saturated solutions of KI, used to treat infectious and inflammatory diseases. The addition of 12-50 mM KI to cultured human peripheral blood mononuclear cells resulted in 319-395 mosM final solute concentration and induced interleukin (IL)-8 synthesis. production was seen when 40 mM salt was added (375 mosM) and was equal to IL-8 induced by endotoxin or IL-la. However, there was no induction of IL-la, IL-118, or tumor necrosis factor to account for the synthesis of IL-8; the effect of KI was not due to contaminating endotoxins. Hyperosmolar NaCl also induced IL-8 and increased steady-state levels of IL-8 mRNA similar to those induced by IL-la. IL-8 gene expression was elevated for 96 hr in peripheral blood mononuclear cells incubated with hyperosmolar NaCl. In human THP-1 macrophagic cells, osmotic stimulation with KI, Nal, or NaCl also induced IL-8 production. IL-1 signal transduction includes the phosphorylation of the p38 mitogen-activated protein kinase that is observed following osmotic stress. Using specific blockade of this kinase, a dose-response inhibition of hyperosmolar NaCl-induced IL-8 synthesis was observed, similar to that in cells stimulated with IL-1. Thus, these studies suggest that IL-1 and osmotic shock utilize the same mitogen-activated protein kinase for signal transduction and IL-8 synthesis.We began these studies to investigate whether KI modulated host defenses, particularly cytokine production. Compounds containing iodine, especially KI, have been used therapeutically for over 100 years to treat inflammatory and infectious diseases such as asthma, gout, gangrene, tertiary syphilis, and mycobacterial and fungal infections (reviewed in ref. 1). Oral KI is currently the treatment of choice for cutaneous sporotrichosis, although KI possesses no intrinsic antibacterial activity. It therefore seemed reasonable that KI could affect host phagocytic cells. In preliminary studies, we reported that the addition of 40 mM KI to cultured human peripheral blood mononuclear cells (PBMC), resulting in a final osmolarity of 375 mosmol/liter (mosM), induced interleukin (IL)-8 synthesis (2). As these studies expanded, we observed that similar concentrations of Nal or NaCl. were equally effective in inducing IL-8 synthesis and, therefore, hyperosmolarity rather than the presence of iodide was likely stimulating the production of IL-8.Mammalian cells are exposed to hyperosmotic conditions in the distal tubule of the kidney, during hemo-or peritoneal dialysis, when serum sodium rises as a consequence of dehydration, and when infused with hypertonic saline (3). In the present studies, we have examined the effect of hyperosmotic conditions on cytokine production. During the course of these studies, it was reported that mammalian cells phosphorylate proteins in response to 200 mM NaCl (400 mosM) (4, 5). Moreover, phosphorylation of a specific p38 mitogen-activatedThe publication costs of this article were defrayed in part by page...

show abstract

“…At the end of the 1980s, it was demonstrated that the high concentrations of acetate contained in acetate dialyses promoted the production of various cytokines by activated monocytes [13,14]. This also seems to be the case even with the much lower concentrations of acetate in bicarbonate haemodialysis, a technique in which an increase of TNF synthesis [2], plasma levels of IL-1b [4], activity of nitric oxide synthetase [2,3] and activation of polymorphonucleates and monocytes [4] have been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

On-line haemodiafiltration with and without acetate

Pizzarelli

Cerrai

Dattolo

et al. 2006

Nephrology Dialysis Transplantation

View full text Add to dashboard Cite

Background. In patients on on-line convective treatments, given the considerable quantity of dialysis fluid re-infused, the small amount of acetate present in bicarbonate dialysis fluid as a pH stabilizing factor may allow a significant transfer of that anion to the patient, possibly inducing cytokine activation. Methods. To verify this hypothesis, we performed on-line haemodiafiltration (OL-HDF) with (3 mmol/l) and without acetate in dialysis fluid in a cross-over randomized order on 12 prevalent patients. Results. In comparison with the pre-treatment values, plasma acetate levels were unchanged during and after acetate-free OL-HDF, while they were 5-6 times higher in the course of OL-HDF containing acetate in dialysis fluid; plasma acetate levels returned to basal values 2 h after the end of the procedure. The total increase of bases in the patient attributable to acetate was 36%.Plasma bicarbonate values at the end of treatment were significantly lower in treatments without acetate, as compared to those with acetate. Interleukin-6 plasma levels were super-imposable at the beginning and in the course of the two methods compared, but there was a tendency towards a greater increase at an interval of 2 h following OL-HDF with acetate. Conclusions. Our preliminary results confirm the assumption that body gain of acetate is particularly high in convective treatments, while acetate-free OL-HDF slows down acetate burden. Clinical advantages due to these effects should be evaluated in properly designed prospective studies.

show abstract

Enhancement of in-Vitro Human Interleukin-1 Production by Sodium Acetate

Cited by 138 publications

References 15 publications

Remarkable Removal of Beta-2-Microglobulin by On-Line Hemodiafiltration

Remarkable Removal of Beta-2-Microglobulin by On-Line Hemodiafiltration

Osmotic regulation of cytokine synthesis in vitro.

On-line haemodiafiltration with and without acetate

Contact Info

Product

Resources

About