Lack of plasma interleukin-1β or tumor necrosis factor-α elevation during unfavorable hemodialysis conditions (original) (raw)
Cellular & molecular immunology
Cytokines are essential mediators of immune response and inflammatory reactions. Patients with chronic renal failure (CRF) commonly present with abnormalities of immune function related with impaired kidney function and the accumulation of uremic toxins in addition to bioincompatibility of dialyzer membranes. During a hemodialysis (HD) session, cytokines are released mainly by monocytes activated by endotoxin-type compounds in dialyzer fluid, complement factors and direct contact with dialyzer membrane. The study included 15 CRF patients, aged 36.4 +/- 2.9 years, on regular HD maintenance therapy for mean 68 +/- 10 months and 15 healthy controls. It was designed to assess serum levels of a panel of inflammatory cytokines: IL-1beta, IL-2, IL-6, IL-8 and TNF-alpha in CRF patients on regular maintenance HD before, 20, 60 and 240 minutes of a single HD session in parallel with C-reactive protein (CRP) as an additional parameter. CRP concentration was increased in HD patients when compar...
The International Journal of Artificial Organs, 1992
Conflicting results have been published concerning the systemic induction of the cytokine tumor necrosis factor alpha (TNFα) during hemodialysis (HD). We therefore evaluated in vitro TNFα production in whole blood as well as in vivo variability of TNFα levels in patients on long-term HD. Whole blood was incubated at room temperature (RT) with or without exogenously added endotoxin (ET), and plasma-TNFα was measured after 5, 30, 120, 240, and 960 min by specific enzyme immunoassay. Additionally, plasma-TNFα before and after 120 and 240 min HD was studied longitudinally once a week over a period of 4 weeks in 36 patients on Cuprophan®(CU, n=23) or polysulfone-F60 (PSu, n=13) HD. Mean plasma TNFα levels in vitro rose from (mean) 8 pg/ml after 5 min to 12 pg/ml (120′) and 32 pg/ml (960′) even without ET addition, and to 18 pg/ml (after 120′) and 88 pg/ml (after 960′) when 0.1 μg/ml ET were added. Pre-dialytic as well as intradialytic TNFα levels in patients showed high intra-individual ...
Renal Failure, 2000
The relationship between production of IL-1b and TNFa by peripheral blood mononuclear cells (PBMC) of hemodialysis (HD) patients and clinical disorders characteristic for HD patients was examined. The study included 28 HD patients divided in the 4 groups: group 1 -6 patients with malnutrition; group 2 -6 patients with secondary hyperparathyroidism; group 3 -6 patients with eosinophilia; group 4 -10 stable HD patients without clinical complication. The control group consisted of 9 healthy volunteers. All patients were dialyzed with cuprophane membrane more than one years. Blood samples were taken immediately before the beginning of hemodialysis and PBMC were isolated by centrifugation on the density gradient. Concentrations of IL-1b and TNFa were measured in the supernatants of the cultures by ELISA tests. The results showed marked individual dierences in cytokine production both in healthy controls and in HD patients. Spontaneous and LPS stimulated production of IL-1b by PBMC of HD patients was signi®cantly higher 195
In vivo induction of interleukin-1 during hemodialysis
Kidney International, 1989
In vivo induction of interleukin-1 during hemodialysis. In vivo induction of interleukin-1 (IL-i) production during hemodialysis was investigated by measuring IL-I 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 (TO) monocyteassociated IL-i 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/mi; P <0.0025) and in non-dialyzed patients with chronic renal failure (0.95 0.85 U/ml, P < 0.0001). Cell-associated IL-i activity was consistently increased after five hours of dialysis with cuprophane membranes (42.4 5.5 U/mI, P < 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 cellassociated IL-i and no complement activation occurred. However, the mean predialytic values of monocyte-associated IL-I in these patients (that is, 32.9 5.6 U/mI and 38 5.65 U/mI for the polyacrylonitrile and the polysulfone groups, respectively) were higher than the predialytic levels of cell-associated IL-I in the patients from the cuprophane group (P < 0.0025). Monocytes obtained at the beginning and five hours of dialysis from patients dialyzed with polyacryionitrile devices, and monocytes obtained at five hours but not at the beginning of dialysis from patients dialyzed with cuprophane membranes, spontaneously released extracellular IL-I after 24 hours of culture in serum free conditions. Neither polyacrylonitrile nor cuprophane differed in their capacity to stimulate monocytes that had adhered to the membrane, to produce IL-l in serum free cultures. These results indicate that IL-I is transiently generated during hemodialysis with complement activating membranes when C3aiC3adesArg and CsaiC5adesArg, which are known inducers of IL-i production, are generated in plasma. Noncomplement dependent factors, possibly LPS or fragments of LPS that often contaminate bicarbonate dialysates, may be responsible for chronic stimulation of IL-1 production in patients dialyzed with high permeability membranes.
Immune System Dysfunction and Inflammation in Hemodialysis Patients: Two Sides of the Same Coin
Journal of Clinical Medicine
Biocompatibility in hemodialysis (HD) has considerably improved in recent decades, but remains an open issue to be solved, appearing essential to reduce systemic inflammation and enhance patients’ clinical outcomes. Clotting prevention, reduction in complement and leukocyte activation, and improvement of antioxidant effect represent the main goals. This review aims to analyze the different pathways involved in HD patients, leading to immune system dysfunction and inflammation. In particular, we mostly review the evidence about thrombogenicity, which probably represents the most important characteristic of bio-incompatibility. Platelet activation is one of the first steps occurring in HD patients, determining several events causing chronic sub-clinical inflammation and immune dysfunction involvement. Moreover, oxidative stress processes, resulting from a loss of balance between pro-oxidant factors and antioxidant mechanisms, have been described, highlighting the link with inflammatio...
Inflammatory signals associated with hemodialysis
Kidney …, 2002
Inflammatory signals associated with hemodialysis. excretion of cytokines, and certain co-morbid condition Background. Inflammation is highly prevalent in chronic he-[6-8]. The hemodialysis procedure has also been sugmodialysis patients. Because hemodialysis involves the contact gested as a potential source of inflammation in chronic of blood with "foreign" surfaces, and the documented activahemodialysis patients. tion of several humoral and cellular pathways during the pro-Several reports have documented the catabolic effects cedure, the hemodialysis procedure has been suggested as a potential source of inflammation in this patient population. Earof a hemodialysis procedure [9, 10]. This effect has been lier studies did not provide clear-cut evidence of the potential explained by the loss of amino acids and protein into the contribution of the hemodialysis procedure to inflammation, dialysate and by the blood-membrane interaction [11, 12]. as assessed by markers of inflammation such as cytokine levels Earlier studies have shown modest changes in selected and acute-phase protein production. cytokine concentrations before and after hemodialysis, Methods. Nine patients were studied using primed-constant infusion of l-(l-13 C) leucine 2 hours before, during, and 2 hours particularly with the use of bioincompatible membranes after a single hemodialysis session. We evaluated the effects [13-21]. Direct evidence of acute-phase response to the of hemodialysis on induction of interleukin-6 (IL-6) production hemodialysis procedure, especially with the use of bioas well as the fractional synthetic rates (FSR) of albumin and compatible hemodialysis membranes, is controversial. In fibrinogen, two well-known acute-phase proteins. Results. During hemodialysis, albumin FSR and fibrinogen order to explore this issue further, we evaluated the direct FSR increased significantly compared to the measurements effects of the hemodialysis procedure on the induction obtained during baseline period. During this period, albumin of inflammatory reaction by serial assessments of interand fibrinogen FSR increased 64% and 34%, respectively, comleukin-6 (IL-6) concentration and the fractional synthetic pared to baseline (P Ͻ 0.05). While the increase in IL-6 conrates (FSR) of two acute-phase reactants, namely serum centration was modest during hemodialysis (14%), the levels further increased at the end of the 2-hour post-hemodialysis albumin and serum fibrinogen before, during, and after period (68% higher compared to baseline, P Ͻ 0.05). Fibrinohemodialysis. IL-6 is considered to be a major regulator gen FSR also demonstrated a further increase during the postof many of the acute phase proteins including C-reactive dialysis period (17% higher compared to the intradialytic peprotein (CRP), albumin, and fibrinogen [22-24]. In addiriod and 58% higher compared to baseline), while albumin FSR tion, fibrinogen levels are often elevated in hemodialysis stabilized during this period. Conclusions. The results provide clear evidence of hemodi-patients and have been found to predict mortality [3, alysis-induced inflammatory response. The process is most no-25, 26]. Of note, fibrinogen FSR is increased in trauma table during the 2-hour post-hemodialysis period. patients who have high levels of inflammatory markers [27]. The results of our study indicate that the hemodialysis procedure induces an inflammatory response as evi-Chronic inflammation is highly prevalent in end-stage denced by the increase in fibrinogen FSR observed durrenal disease (ESRD) patients [1-3]. It is also strongly ing hemodialysis followed by concomitant increases in correlated with clinical outcome [3-5]. Chronic inflamboth IL-6 concentrations and fibrinogen FSR during the mation can be related to multiple factors in ESRD pa-2-hour post-hemodialysis period. tients, including underlying uremic conditions, reduced METHODS
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2002
It has been suggested that changes in immune response to infectious agents in patients on haemodialysis might be due to impaired monocyte function; uraemic and haemodialysed patients overproduce proinflammatory cytokines, such as interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). We quantitated the cytokines released into the plasma and into the supernatants of 24-h cultured purified monocytes, under basal conditions and after stimulation by lipopolysaccharide from Escherichia coli, in 15 healthy subjects (CON), 20 uraemic patients who had not yet started dialysis (CRF) and 60 haemodialysed patients (HD), who were divided into three groups of 20 patients corresponding to short-, medium- and long-term dialysis. Monocytes from HD patients spontaneously secreted significantly higher levels of cytokines than those from controls and uraemic patients who had not yet started dialysis. After stimulation with lipopolysaccharide (LPS), cytokine le...
Kidney International, 1994
Plasma levels of IL-113, TNFa and their specific inhibitors in undialyzed chronic renal failure, CAPD and hemodialysis patients. The presence of naturally occurring inhibitors of interleukin-1 (IL-l) and tumor necrosis factor (TNF) in a variety of diseases has been demonstrated. The IL-i receptor antagonist (IL-IRa) binds to IL-i receptors and blocks the activity of IL-l, and a soluble form of the p55 TNF receptor (TNF5Rp55) binds and neutralizes TNF. In the present study, plasma levels of IL-l/3, IL-iRa, TNFa and TNFsRp55 were measured in 29 undialyzed patients with chronic renal failure (CRF), 13 patients on continuous ambulatory peritoneal dialysis (CAPD), 42 patients on chronic hemodialysis (HD) and in 15 healthy controls. Of the 29 patients with CRF, 13 had end-stage renal disease (ESRD, estimated GFR < 10 mi/mm). Among healthy controls, plasma levels of IL-l/3, IL-IRa and TNFa were at or below the limit of detection of the assay. In undialyzed patients with ESRD, or in patients on CAPD or HD, plasma levels of IL-i/3 were 428 134 pg/mi, 378 83 and 352 43 pg/mI, respectively. Although plasma levels of IL-1f3 in each group of patients were higher than those in healthy controls (<160 pg/mi), these differences were not statistically significant. In contrast, plasma levels of IL-lRa in undialyzed patients with ESRD (629 125 pg/mi, P = 0.03), CAPD (902 164 pg/ml, P < 0.0001) and HD patients (642 73 pg/ml, P = 0.004) were significantly higher than those in healthy controls (103 15). In the same groups, plasma TNFa levels were 1,419 434 pg/ml, 872 267 pg/mi and 803 241 pg/mI, respectively. Although plasma levels of TNFx in all three groups of patients with chronic renal failure were also higher than those in controls (<160 pg/mI), these differences were not statistically significant. Plasma levels of TNFsRp5S in undialyzed patients with ESRD, or in patients on CAPD or HD, were 12,754 2235 pg/ml, 13,373 1,815 pg/nil and 16,750 830 pg/mI, respectively. These levels were significantly higher (P < 0.001) than those in healthy controls (1,695 94 pg/mI). The differences in IL-l/3, IL-IRa, TNFa or TNFsRp55 between the three groups of patients were not statistically significant. The molar ratios of plasma IL-lRa:IL-1j3 in ESRD, CAPD and HD patients were 3 1, 4 I and 4 1, respectively. The molar ratios of plasma TNFsRp55:TNFa ratios in these three groups were 13 3, 21 6 and 38 4, respectively. In undialyzed patients with CRF and healthy controls, regression analysis showed a strong correlation between serum creatinine and plasma levels of IL-iRa (r = 0.497, P = 0.001) or TNFsRp55 (r = 0.737, P < 0.0001). These results demonstrate that plasma levels of IL-1p, TNFa and their specific inhibitors are elevated in both undialyzed patients with ESRD as well as patients on CAPD or HD. The elevated plasma levels of these proteins probably reflect inadequate clearance as well as enhanced production.
Life Sciences, 2005
This work evaluated the phagocytic capacity of monocytes and neutrophils, and tumor necrosis factor-a, interleukin 6, 1 and 8 serum levels in chronic renal failure patients under peritoneal dialysis and hemodialysis treatment, compared with chronic renal failure patients without dialysis treatment and healthy individuals, in order to contribute to a better understanding of the action of these therapies on the evolution of chronic renal failure patients. All patients with chronic renal failure (under dialysis or not) showed decreased phagocytic capacity of neutrophils and monocytes. All those in hemodialysis (cellulose acetate or polysulfone membranes) showed a decreased phagocytic capacity. The phagocytic index for neutrophil was 13 times lower than that of the control group for both membranes, whereas for monocytes, only those using polysulfone membrane showed a significant decrease of 4.9 times in phagocytic capacity. There was an acute stimulation of the phagocytosis by neutrophils after a single session of dialysis with both types of membrane, while only cellulose acetate membrane decreased the phagocytic index of monocytes after the hemodialysis session. Patients using cellulose acetate showed a chronic increase in tumor necrosis factor-a serum levels, while those using polysulfone showed a chronic increase in interleukin 6. After a single hemodialysis procedure, no acute effect of the treatment on tumor necrosis factor-a
Inflammatory Determinants and Associated Morbidity in Hemodialysis Patients
Journal of Personalized Medicine
Hemodialysis deteriorates patients’ physical, metabolic, and mental status. Clinical outcomes derived from inflammation determine a worse status but are less frequently identified. The objective of the study was to identify inflammatory determinants and the effect of SNP-related serum IL-6 and IL-10 levels on associated morbidity in hemodialysis. A sample of hemodialysis patients at IMSS Regional Hospital No.46 in Guadalajara (n = 85) were tested using the Malnutrition Inflammation Score (MIS) and Patient Health Questionnaire-9 (PHQ-9) to assess the associated morbidity. Serum cytokine levels were quantified by enzyme-linked immunosorbent assay (ELISA). The restriction fragment length polymorphism (RFLP) technique was used for analysis of IL-6-572C/G and IL-10-1082A/G. Using data visualization methods, we identified relevant determinants of inflammation. A simple regression model was constructed between predictors and targets with genotypes as covariates. Results showed malnutrition...
Effect of a Hemodialysis Session on Markers of Inflammation and Endotoxin
International Journal of Inflammation, 2022
Background. People receiving hemodialysis (HD) treatment have higher cardiovascular morbidity and mortality, ascribed to an increased prevalence of traditional cardiovascular risk factors. However, the role of nontraditional risk factors, such as inflammation, has become increasingly recognized. The origin of this inflammation remains elusive and one putative cause is elevated levels of circulating bacterial endotoxin. Methods. In this study, serum concentrations of endotoxin and inflammatory biomarkers, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-1β (IL1β), ferritin and tumor necrosis factor (TNF), were measured in 30 adults receiving HD and 10 healthy individuals without kidney disease. In people receiving HD, samples were collected immediately before dialysis (preHD), after dialysis (postHD), and 48 hours after (postHD48hrs). Results. Endotoxin was detectable in only 1 of 90 samples analyzed. There were no significant differences in se...
Cytokine Release and Serum Lipoprotein (a) Alterations During Hemodialysis
Artificial Organs, 2000
It has been reported recently that a number of cytokines, mainly tumor necrosis factor ␣ (TNF␣), interleukin (IL)-1, and IL-6, can alter lipid metabolism and produce hyperlipidemia. Studies in hemodialysis (HD) patients have demonstrated increased production of these cytokines during HD. In order to investigate any possible relationship between changes of cytokines and lipid concentrations during HD in the serum of 25 uremic patients on chronic HD using modified cellulose membranes, TNF␣, IL-1, IL-6, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), lowdensity lipoprotein cholesterol (LDL-C), lipoprotein a (Lp[a]), and total proteins were measured immediately before (pre-HD) and after HD (post-HD), in one session. The post-HD values were corrected according to the hemoconcentration based on the changes in serum total proteins. Serum TNF␣ and IL-1 levels were significantly increased from 38.24 ± 17.85 pg/ml and 2.60 ± 3.64 pg/ml
Exploring Inflammation in Hemodialysis Patients: Persistent and Superimposed Inflammation
Kidney and Blood Pressure Research, 2004
Background: Inflammation is frequently elevated, and seems to be episodic in hemodialysis (HD) patients. Whether, its episodic character is due to the temporal variability, in periods free of clinical events, of the inflammatory indices or due, to the acute phase response induced by common inflammatory stimuli, has not been investigated yet in a longitudinal study. This study explores inflammation forms, characteristics and causes which are probably related to the high cardiovascular disease (CVD) morbidity in HD patients. Methods: In 37 HD patients, high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA) and interleukin-6 (IL-6) were weekly measured for 16 consecutive weeks. Inflammatory clinical events, in the week before every measurement, were recorded. Repeated measures ANOVA were applied for statistical analysis. Results: Fifty-one of 533 patient-weeks were positive for a clinical event. Mean ± SD (range) hs-CRP was 7.01 ± 16.06 (0.2–169) mg/l for all the weeks of ...