We examined whether the synthesis of inter leukin-1 or tumor necrosis factor, two cytokines with po tent inflammatory activities, is influenced by dietary sup plementation with n -3 fatty acids.Nine healthy volunteers added 18 g of fish-oil concen trate per day to their normal Western diet for six weeks. We used a radioimmunoassay to measure interleukin-1 (IL-1/3 and IL-1 a) and tumor necrosis factor produced in vitro by stimulated peripheral-blood mononuclear cells. With endotoxin as a stimulus, the synthesis of IL-1/3 was suppressed from 7.4±0.9 ng per milliliter at base line to 4.2±0.5 ng per milliliter after six weeks of supplementa tion (43 percent decrease; P = 0.048). Ten weeks after the end of n -3 supplementation, we observed a further decrease to 2.9±0.5 ng per milliliter (61 percent decrease;

Interleukins (IL) -1 beta and -1 alpha and tumor necrosis factor (TNF-alpha) were measured by radioimmunoassay in plasma samples from 44 healthy individuals, 15 patients in septic shock, and 6 volunteers infused with endotoxin. Plasma IL-1 alpha levels were low (40 pg/ml) or undetectable in all situations. In 67% of the healthy subjects, plasma IL-1 beta levels were less than 70 pg/ml. Septic patients had higher plasma IL-1 beta levels (120 +/- 17 pg/ml, P = .001); those of surviving patients were higher than those of patients who died (P = .05). Plasma TNF-alpha concentrations in septic individuals were elevated (119 +/- 30 pg/ml) and correlated with severity of illness (r = .73, P = .003), but no correlation was observed between plasma IL-1 beta and TNF-alpha concentrations in individual samples. Infusion of endotoxin caused a twofold elevation of IL-1 beta, from a baseline of 35 +/- 5 pg/ml to a maximum of 69 +/- 27 pg/ml at 180 min (P less than .05). Peak TNF-alpha levels after endotoxin infusion were 15 times higher than IL-1 beta levels, were attained more rapidly (90 min), and as with the septic patients, did not correlate with IL-1 beta levels. These data support the concept that plasma IL-1 beta and TNF-alpha concentrations are regulated independently and are associated with different clinical outcomes.

In patients with septic shock, coupled plasmafiltration-adsorption combined with hemodialysis was associated with improved hemodynamics compared with continuous venovenous hemodiafiltration. This result might be related to its ability to restore leukocyte responsiveness to lipopolysaccharide. These findings suggest a potential role for blood purification in the treatment of septic shock.

Reimbursement for chronic dialysis consumes a substantial portion of healthcare costs for a relatively small proportion of the total population. Each country has a unique reimbursement system that attempts to control rising costs. Thus, comparing the reimbursement systems between countries might be helpful to find solutions to minimize costs to society without jeopardizing quality of treatment and outcomes. We conducted a survey of seven countries to compare crude reimbursement for various dialysis modalities and evaluated additional factors, such as inclusion of drugs or physician payments in the reimbursement package, adjustment in rates for specific patient subgroups, and pay for performance therapeutic thresholds. The comparison examines the United States, the province of Ontario in Canada, and five European countries (Belgium, France, Germany, The Netherlands, and the United Kingdom). Important differences between countries exist, resulting in as much as a 3.3-fold difference between highest and lowest reimbursement rates for chronic hemodialysis. Differences persist even when our data were adjusted for per capita gross domestic product. Reimbursement for peritoneal dialysis is lower in most countries except Germany and the United States. The United Kingdom is the only country that has implemented an incentive if patients use an arteriovenous fistula. Although home hemodialysis (prolonged or daily dialysis) allows greater flexibility and better patient outcomes, reimbursement is only incentivized in The Netherlands. Unfortunately, it is not yet clear that such differences save money or improve quality of care. Future research should focus on directly testing both outcomes.

We have demonstrated that purified C5a is a potent stimulus to human PBMC secretion of TNF-alpha, IL-1 beta, and IL-1 alpha, which proceeds in a dose-dependent fashion. At a given concentration of C5a, TNF-alpha and IL-1 beta secretion did not differ significantly; both were secreted in significantly greater quantity than IL-1 alpha. Clinical conditions such as Gram-positive and Gram-negative bacterial infections, trauma, and immune complex diseases activate complement. Through the mediation of TNF and IL-1 secreted in response to C5a, these diverse disorders can share common features of fever, coagulopathy, acute phase protein production, and disordered metabolism.

Pro-inflammatory cytokine-inducing substances derived from cultured E. coli have previously been shown to pass across low-flux regenerated cellulosic dialyzer membranes. In the present study, a sterile filtrate of Pseudomonas maltophilia grown from standard bicarbonate dialysis fluid was used to test the permeability of various dialyzer membranes (regenerated cellulose, cellulose triacetate, polyacrylonitrile, polysulfone and polyamide) to TNF alpha-inducing bacterial substances. Pyrogen-free tissue culture medium (MEM) was recirculated for 60 minutes in the dialysate compartment of a closed-loop dialysis system, then P. maltophilia filtrate was added and recirculation was continued for a further hour. Samples from the dialysate (MEM) and the blood side (containing 10% human plasma in MEM) were incubated with donor mononuclear cells (MNC) for 18 hours and TNF alpha release was measured in MNC supernatants by radioimmunoassay. Five minutes after the addition of P. maltophilia filtrate, mean TNF alpha-inducing activity in the dialysate increased from (mean +/- SEM) 0.10 +/- 0.02 to 18.2 +2- 1.5 (ng/2.5 x 10(6) MNC/18 hr). TNF alpha-inducing activity in the blood side increased with regenerated cellulose from 0.10 +/- 0.01 to 4.57 +/- 1.55 (N = 8; P less than 0.001); with cellulose triacetate from 0.20 +/- 0.05 to 0.44 +/- 0.10 (N = 5; P less than 0.05), and with polyacrylonitrile from 0.10 +/- 0.02 to 1.16 +/- 0.45 (N = 5; P less than 0.03). No increased TNF alpha-inducing activity was observed in the blood side of polysulfone (N = 5) or polyamide dialyzers (N = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

No abstract