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Biomedical subjects

B Descamps-Latscha

Publications and source records attributed to B Descamps-Latscha.

At least 55 records · Page 3Linked to original sources
PubMed1995

[Dysregulation of the immune system in chronic uremic and hemodialysed patients].

Concomitant immune deficiency and activation of immuno-competent cells, together with a disequilibrium between inflammation-inducing cytokines and their specific natural inhibitors is the basis of our current understanding of immune system dysregulation in patients with chronic uraemia. These anomalies may even be accentuated by dialysis. Clinically, bacterial infections, viral hepatitis and amyloidosis all play important roles. Humoral factors include abnormal immunoglobulin response to specific antibodies and complement activation. The response of T lymphocytes, long sought as the origin of the immunodeficiency associated with chronic uraemia, is also significantly decreased in these patients. The decreased antibody responses to specific stimuli may be related to B cell dysfunction. Monocyte and polymorphonuclear cell reactions are also perturbed. A deficiency in natural killer cells is observed although the mechanisms involved and the consequences are still debated. The factors determining the anomalies leading to immune system dysregulation in chronic uraemia and dialysis and their relationship with the reduction in active nephron mass as well as their metabolic and/or endocrine consequences remain to be fully described. A better understanding of the mechanisms involved should lead to new strategies for immuno-intervention in patients with chronic renal failure and help in optimizing haemodialysis.

Chronic Disease↗
PubMed1995

Balance between IL-1 beta, TNF-alpha, and their specific inhibitors in chronic renal failure and maintenance dialysis. Relationships with activation markers of T cells, B cells, and monocytes.

Patients with end-stage renal disease present an immunodeficiency that paradoxically coexists with activation of most immunocompetent cells, and the roles of chronic uremia and maintenance dialysis are poorly understood. We determined circulating levels of IL-1 beta and IL-1Ra, TNF-alpha and its soluble receptors (TNF-sR55 and TNF-sR75), and activation markers of T cells (soluble CD25), B cells (soluble CD23), and monocytes (neopterin) in a large cohort of undialyzed patients at various stages of chronic renal failure and in dialyzed patients on maintenance hemodialysis or chronic peritoneal dialysis. The progression of uremia was associated with a gradual increase in soluble CD25, CD23, and especially neopterin levels. Although IL-1 beta could not be detected, IL-1Ra levels were significantly increased from the earliest stage of renal failure. Plasma levels of TNF-alpha, TNF-sR55, and TNF-sR75 progressed with the severity of renal failure and correlated with soluble CD25, CD23, and neopterin levels, whereas IL-1Ra levels correlated exclusively with TNF-sR55 levels. Compared with undialyzed patients, levels of IL-1 beta were higher in patients on maintenance hemodialysis, whereas those of IL-1Ra were lower and decreased further at the end of dialysis sessions. In contrast, both TNF-sR55 and TNF-sR75 levels were significantly higher than in undialyzed patients and increased further at the end of dialysis sessions in the absence of an increase of TNF-alpha. Such an imbalance between cytokines and their inhibitors may play a pivotal role in the multifaceted process of immune dysfunction.

B-Lymphocytes↗
PubMed1995

Neutrophil-derived long-lived oxidants in cystic fibrosis sputum.

We evaluated long-lived oxidant potential in the sputum of patients with cystic fibrosis (CF) by quantitating the methionine-inhibitable, long-lived oxidant fraction of sputum, referred to as the chloramines. Taurine, the preferred amino acid substrate for chloramine formation, and myeloperoxidase (MPO), the chlorinated oxidant-generating enzyme, were also quantitated. As compared with the sputum of asthmatic subjects, the sputum of CF patients contained high concentrations of chloramines along with high levels of taurine and active MPO. A negative correlation between chloramine and taurine was found in the sputum of CF patients. No correlation was found between the density of Pseudomonas aeruginosa and the level of chloramines, taurine, or MPO. In contrast, respiratory parameters (%FEV or %FVC) and a nutritional index correlated positively with chloramine levels, whereas negative correlations were observed with taurine and MPO. In addition, the effect of antibiotic therapy, which significantly increased chloramine and decreased taurine levels, supported a beneficial effect of chloramines on overall clinical status. Our findings support a dual role of long-lived oxidants at the site of airway inflammation in CF, one component of which is their ability to mediate oxidative stress and the other a beneficial effect that may be partly explained by their inhibitory effect on antiprotease defense systems.

Adolescent↗
PubMed1995

Progression rate to end-stage renal failure in non-diabetic kidney diseases: a multivariate analysis of determinant factors.

BACKGROUND: The respective contribution of the type of nephropathy, gender, and proteinuria, and of the potentially alterable factors blood pressure level and daily protein intake on the rate of progression in non-diabetic renal diseases is debated. METHODS: We retrospectively analysed the influence of primary renal disease, gender, urinary protein excretion, mean arterial pressure (MAP), and dietary protein intake on the rate of decline in creatinine clearance (delta Ccr) in 159 adult patients with well-defined nondiabetic kidney diseases. All patients had been followed from a baseline Crr of 40-50 ml/min/1.73 m2 until endstage renal disease and need for dialysis. RESULTS: Mean (+/- SD) delta Ccr (ml/min/1.73 m2/year) was 9.9 +/- 6.5 in 51 patients (45 males) with chronic glomerulonephritis, 6 +/- 2.5 in 50 patients (26 males) with polycystic kidney disease, 5.5 +/- 2.4 in 17 patients (16 males) with hypertensive angionephrosclerosis, and 3.9 +/- 2 in 41 patients (21 males) with chronic tubulointerstitial nephritis. delta Ccr was higher in males than in females (7.5 +/- 5.2 versus 4.8 +/- 2.5; P < 0.001). Linear regression analysis of the whole population disclosed a strong relationship between delta Ccr and proteinuria (r2 = 0.23; P < 0.001), and a weak relationship between delta Ccr and protein intake (r2 = 0.03; P = 0.02), but no relationship between delta Ccr and MAP (r2 = 0.01; P = 0.23). Stepwise multiple regression analysis identified the type of nephropathy, gender, and proteinuria as independent predictive factors of progression; however, these factors together accounted for only 36% of the variation in delta Ccr, suggesting the contribution of other yet unidentified factors. CONCLUSIONS: Primary kidney disease and urinary protein excretion (reflecting the severity of renal disease in individual cases) appear as the major determinants of the rate of progression, with faster progression in males in all types of nephropathy, whereas potentially alterable factors such as blood pressure and protein intake had only a modest influence in the range of values observed in our patients.

Adult↗
PubMed1994

Soluble CD23 potentiates interleukin-1-induced secretion of interleukin-6 and interleukin-1 receptor antagonist by human monocytes.

The low-affinity receptor for IgE (CD23) is cleaved into biologically active soluble fragments (sCD23), some of which have been reported to exhibit pleiotropic activities. However, it is not known whether the sCD23 fragments contribute to the induction and/or regulation of pro-inflammatory cytokine production. In this study, this possibility was tested using interleukin (IL)-1-stimulated human whole blood as an ex vivo model of cytokine cascade production. We show that human recombinant 25-kDa sCD23 significantly enhanced the production of IL-6 in whole blood stimulated by IL-1, but had only little or no effect in the absence of IL-1. The potentiating effect of sCD23 was concentration dependent within the range of plasma levels occurring during various inflammatory processes in man. These results prompted us to study whether sCD23 and IL-1 together also enhance the production of regulating factors exhibiting anti-cytokine activities. Our data indicate that sCD23 augments the release of IL-1 receptor antagonist induced by IL-1. Finally, examining the effect of sCD23 on human peripheral monocytes stimulated by IL-1, we confirmed the capacity of sCD23 to potentiate cytokine production. We suggest that sCD23 can modulate monocyte functions, thereby contributing to the amplification and regulation of immune and inflammatory processes.

Enzyme-Linked Immunosorbent Assay↗
PubMed1994

Induction of soluble tumor necrosis factor receptor (sTNF-R75) release by HIV adsorption on cultured human monocytes.

Soluble tumor necrosis factor (TNF) receptors were recently detected in the circulation of patients with early HIV-induced disease, at significantly higher levels than in control subjects. They were proposed as markers of disease progression and of the degree of immunodeficiency. We report that adsorption of heat-inactivated HIV-1 LAI to isolated human monocytes triggers the release of both TNF-alpha and its natural specific inhibitor, the soluble TNF receptor (sTNF-R)75, but not that of sTNF-R55. Only limited inhibition of sTNF-R release was obtained in the presence of a fully neutralizing anti-TNF-alpha monoclonal antibody, suggesting that stimulation by TNF-alpha was only partially responsible for sTNF-R release. HIV-1 LAI induced a higher sTNF-R/TNF ratio than lipopolysaccharide, a well-known monocyte activator. Monocytes thus represent a cellular source of sTNF-R that can be detected in the circulation of HIV-infected patients from seroconversion onwards. The release of sTNF-R could be of great significance in the control of HIV infection via the cytokine network and especially TNF-alpha.

HIV Infections↗
PubMed1993

Soluble CD23 as an effector of immune dysregulation in chronic uremia and dialysis.

Patients with chronic renal failure often present an immunodeficiency state paradoxically exacerbated by hemodialysis and associated with signs of T cell activation. The presence of circulating monokines suggests that monocytes are also activated. Whether or not this includes B cells is controversial, despite frequently abnormal antibody responses. We thus investigated whether the soluble low-affinity receptor for IgE (Fc epsilon RII/CD23), recently identified as a marker of B cell and monocyte activation and possibly involved in T cell activation, was modulated by chronic renal failure and hemodialysis. Relative to values in healthy individuals (N = 31), plasma concentrations of soluble CD23 were significantly elevated in non-dialyzed chronically uremic patients (N = 44), more elevated in patients on peritoneal dialysis (N = 24), and most elevated in those on regular hemodialysis (N = 132), stabilizing after about six months. Soluble CD23 levels were unmodified by the first dialysis session but rose markedly during regular dialysis with cellulose or polysulfone membranes, but not with polyacrilonitrile AN-69 membranes. Soluble CD23 levels correlated with levels of IgG, and those of tumor necrosis factor alpha and interleukin-6, suggesting that increased sCD23 levels reflect activation of B cells and monocytes, respectively. These findings reinforce the view of soluble CD23 as a multi-functional receptor/cytokine, and provide evidence that it might contribute to the immune dysregulation associated with chronic renal failure and exacerbated by hemodialysis.

Adolescent↗
PubMed1993

The immune system in end-stage renal disease.

Patients with end-stage renal disease present with an immunodeficient state paradoxically coexisting with signs of activation of immune system cells and that is accentuated rather than corrected by replacement dialysis therapy. The mechanisms of this immune system dysregulation presently under consideration are a reduced bioavailability of interleukin-2 secondary to its overconsumption by activated T cells; a downregulation of phagocyte adhesion molecules and opsonin receptors following their overexpression during dialysis with complement-activating membranes; an increased production of the cytokines interleukin-1, tumor necrosis factor-alpha, and interleukin-6 by activated monocytes and of soluble CD23 by B lymphocytes; and last, but far from least, the presence of uremic toxins. Perspectives of research are aimed at elucidating the respective role of the T helper cell subpopulations (Th-1 and Th-2) and the influence of the progression of chronic renal failure on the naturally occurring cytokine inhibitors, with the hope of better defining the rationale of strategies of immunomodulation that could be beneficial to patients with end-stage renal disease.

Antibody Formation↗
PubMed1993

Modulation of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-8, and granulocyte/macrophage colony-stimulating factor expression in human monocytes by an endogenous anxiogenic benzodiazepine ligand, triakontatetraneuropeptide: evidence for a role of prostaglandins.

Triakontatetraneuropeptide (TTN) is the major processing product of the endogenous anxiogenic peptide ligand of the benzodiazepine receptor, diazepam binding inhibitor. In the present study, we demonstrated by Northern blot analysis that the mRNA levels for tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, granulocyte/macrophage colony-stimulating factor, IL-6, and IL-8 were significantly increased after 4 hr of incubation of human monocytes with lipopolysaccharide (LPS) and TTN (10(-11) M), compared with cells incubated with LPS alone. Exposure of monocytes for 20 hr to LPS and TTN (10(-11) M) also stimulated TNF-alpha, IL-1 beta and granulocyte/macrophage colony-stimulating factor release by 80%, 110%, and 98%, respectively, relative to the response elicited by LPS alone. Smaller stimulatory effects were observed using the prototypic pharmacological peripheral benzodiazepine Ro5-4864 (10(-11) M) (55%, 72%, and 62%, assessed by means of specific enzyme immunoassays). In contrast, TTN and Ro5-4864 did not modulate LPS-induced IL-6 and IL-8 production. Treatment with the cyclooxygenase inhibitor indomethacin increased IL-1 beta and TNF-alpha secretion but not that of IL-6 or IL-8. The observed stimulatory effects of TTN and indomethacin were not additive. Taken together, these findings suggest a common mechanism of action for TTN and indomethacin, involving PG formation. In this respect, TTN inhibited prostaglandin (PG) E2 production by 30%. The fact that the observed modulatory effects correlated with PG levels suggests the existence of a second-messenger pathway associated with the peripheral-type benzodiazepine receptor. These results indicate that human TTN differentially modulates the LPS-induced expression of proinflammatory cytokines, and they further support the concept that this endogenous psychoactive peptide could be involved in physiological control of the inflammatory response.

Cells, Cultured↗
PubMed1992

Microtiter plate assay for phagocyte-derived taurine-chloramines.

Despite their potential importance, the role of phagocyte-derived chloramines ("long-lived oxidants") has not yet been investigated in inflammatory or infectious diseases. We have developed a sensitive spectrophotometric microtiter plate assay for chloramines based on their capacity to oxidize potassium iodide (KI). Consistent levels of endogenous chloramines were detected in normal human polymorphonuclear neutrophil (PMN) supernatants after stimulation by phorbol myristate acetate (PMA) or opsonized zymosan. Exogenous taurine strongly enhanced chloramine secretion and was used to quantify the chlorinating potential of PMN. Taurine-chloramines were also detectable in monocyte supernatants, although in smaller amounts. The specificity of the KI assay was assessed both in terms of effect of compounds inhibiting (KBr) or interacting with (sodium azide and catalase) chloramine formation and by showing that PMN from patients with chronic granulomatous disease, due to a hereditary lack of oxidative response capacity, were unable to produce chloramines. Taurine-chloramine levels secreted by PMA (but not zymosan)-stimulated PMN were closely related to the cellular luminol-amplified chemiluminescence (CL) responses although the CL assay failed to detect chloramines in PMN supernatants. We consider that this KI assay should be of use in studying the role of long-lived phagocyte-derived oxidants in clinical medicine.

Chloramines↗
PubMed1992

Pholasin: a new chemiluminescent probe for the detection of chloramines derived from human phagocytes.

We have previously reported that normal human polymorphonuclear neutrophils (PMN) release taurine-chloramine, a long-lived oxidant, in response to stimulation by phorbol myristate acetate (PMA) or opsonized zymosan in the presence of exogenous taurine. We now describe a new, simple, and highly sensitive method for the detection of chloramines, including taurine-chloramine, using the chemiluminescent probe Pholasin, the luciferin of the mollusc Pholas dactylus. Taurine-chloramine (N-chlorotaurine) detection was assessed with both a colorimetric method (based on the oxidation of potassium iodide) and with the Pholasin-dependent chemiluminescence (CL) method. The taurine-chloramine concentration in PMN supernatants determined using the potassium iodide (KI) method correlated closely with Pholasin-dependent CL. This CL was also assessed in nonoxidative conditions. No taurine-chloramine was detected in supernatants of lymphocytes and PMN from patients with an oxidative burst defect (chronic granulomatous disease, CGD) with the KI method, but Pholasin-dependent CL was consistently observed. The use of methionine, a specific chloramine scavenger in our incubation conditions, allowed us to define a methionine-inhibitable fraction of Pholasin-dependent CL (i.e., chloramine-induced CL).

Child↗
PubMed1992

Induction of cytokines by dialysis membranes in normal whole blood: a new in vitro assay for evaluating membrane biocompatibility.

We investigated the capacity of cellulose cuprophane (CUP) and synthetic polyacrylonitrile dialysis membranes to induce the production of interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor alpha using an in vitro model in which normal whole blood is incubated directly with calibrated membrane fragments. We found that only CUP membranes significantly increased plasma levels of IL-1, IL-6, and tumor necrosis factor alpha. The participation of lipopolysaccharide was excluded, since its addition to whole blood incubated with CUP led to a synergistic enhancement of IL-1 production, while the addition of polymyxin B had no significant effect. Transfer experiments showed that CUP-pretreated plasma was able to induce cytokine production by autologous monocytes. Inactivation of complement components prior to pretreatment abolished this effect. The participation of complement activation was further revealed by a correlation between cytokine and C5a plasma levels. Lastly, incubation of isolated monocytes with CUP but not with polyacrylonitrile also induced cytokine production, although to a lesser degree. In conclusion, our simple in vitro model can be used to evaluate the biocompatibility of dialysis membranes directly by using whole blood with greater relevance to the in vivo situation than models based on isolated blood components.

Acrylic Resins↗
PubMed1992

Permeability of cellulosic and non-cellulosic membranes to endotoxin subunits and cytokine production during in-vitro haemodialysis.

The possibility of endotoxin transfer across haemodialysis membranes remains a controversial issue. Additional concern has arisen because of the recent introduction in clinical practice of highly permeable, synthetic dialysis membranes and of bacteria-contaminated bicarbonate concentrate with potential short-term and long-term hazards for haemodialysis (HD) patients. Therefore, we performed experiments in an in-vitro dialysis recirculation system using three different types of HD membranes, namely standard regenerated cellulose (Cuprophan, CU), polyacrylonitrile AN-69 (PAN), and polysulphone F-60 (PS). When radiolabelled lipopolysaccharide (125I M-LPS) from E. coli, together with 10 micrograms/ml unlabelled LPS, was added to the recirculating solution in the dialysis compartment, radioactivity could be detected in the blood compartment after 15 min and increased progressively with time up to respectively 6.7% (CU), 10.3% (PAN), and 10.3% (PS) of initial activity on the dialysate side. The addition of albumin to the solution on the blood side led to a decreased permeability of radioactivity (7.3% vs 10.3%), compared to the absence of albumin (tested only for PS membrane). Furthermore, 73% of 125I M-LPS transferred across the PS membrane in the presence of albumin was TCA-precipitable. In contrast, free iodine (Na 125I) incubated in an albumin-containing solution did not precipitate with albumin after the addition of TCA (precipitation of only 0.6%). Moreover, kinetics of transmembranous transfer of Na-125I were strikingly different from that of 125I M-LPS. Analysis by the method of sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of the blood side solution, after LPS addition in the dialysis solution and 30 min of back-filtration, revealed the presence of several silver-stainable and autoradiographic bands of low-molecular-weight range, probably LPS fragments. Finally, the presence of LPS in the dialysate compartment led to a moderate increase in interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF) concentrations in plasma as well as in monocyte culture supernatants after isolation from recirculating normal human whole blood exposed to CU, PAN, or PS membrane. In conclusion, our study provides evidence for the permeation of low-molecular-weight LPS subunits across cellulosic and non-cellulosic HD membranes. The clinical significance, if any, of such a transfer has, however, still to be demonstrated.

Cellulose↗