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PubMed1990

Soluble interleukin-2 receptor and soluble CD8 in serum and cerebrospinal fluid during human immunodeficiency virus-associated neurologic disease.

We have measured levels of soluble interleukin-2 receptor (sIL-2R) and soluble CD8 (sCD8) in serum and cerebrospinal fluid (CSF) of 127 human immunodeficiency virus (HIV)-seropositive and 51 HIV-seronegative individuals. Serum levels of sIL-2R and sCD8 were higher in HIV+ than in HIV- individuals. HIV+ individuals were grouped by neurological status: asymptomatic, abnormal on neuropsychological screening, HIV-related meningitis, inflammatory demyelinating polyneuropathy, opportunistic central nervous system (CNS) infections and HIV-related dementia, myelopathy or sensory neuropathy. Serum levels of sIL-2R and sCD8 were higher in all HIV+ categories compared to HIV- individuals. Patients with HIV-related meningitis had higher levels of sIL-2R and sCD8 than asymptomatic HIV+ individuals, and inflammatory polyneuropathy patients had higher levels of sCD8. CSF levels of sCD8 were higher in all categories of HIV+ than in HIV- individuals. Patients with HIV-related meningitis, inflammatory neuropathy and opportunistic infections had higher levels than asymptomatic individuals. Examination of the time course showed that serum and CSF levels of sIL-2R and sCD8 increased to very high levels during acute HIV infections. Serum levels then declined over several months to relatively stable elevated levels. By 1-2 years after HIV infection sIL-2R was relatively low in CSF, while sCD8 remained elevated with a gradual decrease over the subsequent years of follow-up.

Antigens, CD↗

PubMed2004

Polyethylene glycol-polyamidoamine dendritic micelle as solubility enhancer and the effect of the length of polyethylene glycol arms on the solubility of pyrene in water.

Unimolecular dendritic micelles designed as solubility enhancers were obtained by coupling polyethylene glycol (PEG) to Starburst polyamidoamine (PAMAM) dendrimers. Micelles-750, -2000, and -5000 have a generation 3.0 dendrimer core (32 primary amine end groups) and PEG arms with molecular weights of 750, 2000, and 5000, respectively. The conjugate of dendrimer core and PEG was characterized by MALDI-TOF MS and 1H NMR. 1H NMR was also used to estimate the average number of PEG arms on each dendrimer molecule. A typical hydrophobic compound, pyrene, was sonicated in an excess amount together with micelles at 50 degrees C for 6 h to produce its saturated water solution. The change of the solubility of pyrene was monitored at 334 nm, its maximum adsorption wavelength, by UV-VIS spectra. Concentrated micelles tended to dissolve more pyrene. However, there is no obvious linear relationship between micelle type and the amount of pyrene entrapped within micelles. Micelle-2000 could solubilize more pyrene than micelle-750. It is hypothesized that micelle-5000 did not solubilize more pyrene than micelle-2000 because of the PEG shell disruption by adjacent interpenetration of individual micelles when PEG arm length increased.

Dendrites↗

PubMed2003

Pseudomonas stutzeri soluble nitrate reductase alphabeta-subunit is a soluble enzyme with a similar electronic structure at the active site as the inner membrane-bound alphabetagamma holoenzyme.

A two-subunit (alphabeta) form of dissimilatory nitrate reductase from Pseudomonas stutzeri strain ZoBell was separated from the membrane-residing gamma-subunit by a heat solubilization step. Here we present an optimized purification protocol leading to a soluble alphabeta form with high specific activity (70 U/mg). The soluble form has the stoichiometry alpha(1)beta(1) consisting of the 130 kDa alpha-subunit and the 58 kDa beta-subunit. We did not observe any proteolytic cleavage in the course of the heat solubilization. The enzyme is competively inhibited by azide, but not by chlorate. It exhibits a K(M) value of 3.2 mM for nitrate. We compare the enzymatic and electron paramagnetic resonance (EPR) spectroscopic properties of the alphabeta form with the alphabetagamma holoenzyme which resides in the membrane and can be prepared by detergent extraction. The nearly identical EPR spectra for the Mo(V) signal of both enzyme preparations show that the active site is unaffected by the heat step. The factors influencing the binding of the alpha- and beta-subunit to the gamma-subunit are discussed.

Azides↗

PubMed2003

Presence of detectable levels of soluble HLA-G molecules in CSF of relapsing-remitting multiple sclerosis: relationship with CSF soluble HLA-I and IL-10 concentrations and MRI findings.

We have investigated the presence of non-classical soluble HLA-G molecules (sHLA-G) in cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients and the possible relationships between CSF levels of sHLA-G, classical soluble HLA-I (sHLA-I) molecules, IL-10 amounts and Magnetic Resonance Imaging (MRI) findings were evaluated. We studied by ELISA technique the sHLA-I, sHLA-G and IL-10 levels in CSF of 50 relapsing-remitting (RR) MS patients stratified according to clinical and MRI evidence of disease activity. Thirty-six patients with other inflammatory neurological disorders (OIND) and 41 with non-inflammatory neurological disorders (NIND) were used as controls. CSF mean levels were significantly higher in MS and OIND than in NIND for sHLA-I (p<0.001) and in MS than in controls for sHLA-G (p<0.001), with no differences among the various groups for IL-10 mean concentrations. An increase in CSF sHLA-I was found in MS patients with Gd-enhancing lesions (p<0.01), while sHLA-G and IL-10 were more represented in MS patients without lesional activity on MRI scans (p<0.02). In MRI-inactive MS, CSF IL-10 mean concentrations were significantly greater in patients with CSF-detectable levels of sHLA-G than in those without any evidence of CSF sHLA-G expression (p<0.05). Our findings suggest that CSF classical sHLA-I and non-classical sHLA-G levels may modulate MS activity as assessed by MRI acting in opposite directions. The association observed between sHLA-G and IL-10 when Gd-enhancing lesion resolved indicates a potential immunoregulatory role for IL-10 in the control of MS disease activity by shifting the sHLA-I/sHLA-G balance towards sHLA-G response.

Adult↗

PubMed1997

Serum levels of specific IgE, soluble interleukin-2 receptor, and soluble intercellular adhesion molecule-1 in seasonal allergic rhinitis.

BACKGROUND: There is increasing evidence that soluble interleukin-2 receptor (sIL-2R) might reflect T cell activation in vivo and soluble intercellular adhesion molecule-1 (sICAM-1) might reflect the ongoing inflammatory response in the inflamed site. OBJECTIVE: The aim of this study was to determine the effect of antihistamine tablets and allergen-specific immunotherapy on the seasonal changes in specific IgE, sIL-2R, and sICAM-1 in the serum of patients with seasonal allergic rhinitis. METHODS: This prospective study included 99 patients with seasonal allergic rhinitis due to Japanese cedar pollens and 27 nonatopic healthy volunteers. The patients were divided into an antihistamine-treated group and an immunotherapy group. Serum samples were collected before and during the pollen season from each patient to determine specific IgE, sIL-2R, and sICAM-1. RESULTS: Levels of sIL-2R before the pollen season did not differ significantly among the nonatopic group, the antihistamine-treated group, and the immunotherapy group. The levels of sICAM-1 before the pollen season were significantly higher in the antihistamine-treated group and in the immunotherapy group than in the nonatopic group. Seasonal increase in specific IgE was significant in the antihistamine-treated group regardless of their clinical outcomes. In contrast, significant increase in specific IgE was observed during the pollen season in poor responders but not in good responders to immunotherapy. Serum levels of sIL-2R and sICAM-1 were significantly increased during the pollen season in poor responders of the antihistamine-treated group and the immunotherapy group. On the other hand, neither seasonal increase in sIL-2R nor sICAM-1 was significant in good responders of the antihistamine-treated group and the immunotherapy group. CONCLUSIONS: Serum levels of sICAM-1 are higher in patients with seasonal allergic rhinitis, even outside of the pollen season when the allergen does not naturally exist. Seasonal changes in serum sICAM-1 as well as sIL-2R and specific IgE are probably objective markers to indicate the clinical efficacy of antihistamines and immunotherapy on seasonal allergic rhinitis.

Adult↗

PubMed2000

Taste active compounds in a goat cheese water-soluble extract. 2. Determination of the relative impact of water-soluble extract components on its taste using omission tests.

The aim of this work was to determine the relative impact of water-soluble compounds on the gustatory properties of a goat cheese water-soluble extract (WSE). Using a semisynthetic model mixture (MWSE) previously elaborated in physicochemical and gustatory accordance with the cheese WSE (see part 1, Engel et al. J. Agric. Food Chem. 2000, 48, 4252-4259), omission tests were performed. Among the main taste characteristics of the WSE (salty, sour, and bitter), saltiness was explained by an additive contribution of sodium, potassium, calcium, and magnesium cations, whereas sourness was mainly due to a synergistic effect involving sodium chloride, phosphates, and lactic acid and bitterness was found to result from calcium and magnesium chlorides, the impact of which was partially masked by sodium chloride. In contrast, amino acids, lactose, and peptides did not have any significant impact on WSE taste properties. To quantify the contribution of the taste active compounds to bitterness and saltiness, stepwise multiple linear regressions were performed. Those contributions were expressed as a percentage of the considered taste characteristic intensity in the WSE. The model obtained allowed up to 97.4% of the perceived saltiness to be described and approximately 85% of the bitterness.

Animals↗

PubMed2003

Soluble E-selectin and soluble ICAM-1 levels as markers of the activity of atopic dermatitis in children.

The expression of adhesion molecules is up-regulated in the skin of atopic dermatitis (AD) patients, and the levels of the soluble adhesion molecules sE-selectin and sICAM-1 have been reported to reflect the endothelial activation in the skin of AD patients. The objective of the study was to investigate the relationship between symptom score and levels of sE-selectin, sICAM-1 and sVCAM-1 before and after 2 weeks of treatment. Eighteen children with an exacerbation of AD were admitted and treated with corticosteroid dilutions under occlusive wet dressings (wet-wrap treatment). Symptom score (objective SCORAD) and levels of sE-selectin, sICAM-1, and sVCAM-1 were assessed before and after 2 weeks of treatment. A significant correlation between the objective SCORAD before treatment and the level of sE-selectin (p < 0.05), but not the level of sICAM-1 (p = 0.7) or sVCAM-1 (p = 0.5) was observed. The treatment resulted in a high degree of remission, which was reflected by a significant decrease in the level of sICAM-1 (p < 0.01), whereas there was only a trend in the level of sE-selectin to decrease (p = 0.08). The level of sE-selectin after 2 weeks of treatment still correlated significantly with the objective SCORAD before treatment (p < 0.005). Soluble E-selectin is a relative objective marker for the severity of AD. SCORAD is a treatment-sensitive symptom of AD, whereas E-selectin may be a more stable underlying systemic representation of AD.

Administration, Inhalation↗

PubMed2002

Weight loss increases soluble leptin receptor levels and the soluble receptor bound fraction of leptin.

OBJECTIVE: Soluble leptin receptor (sOB-R) represents the main binding site for leptin in human blood. The aim of this study was to investigate the relationship between leptin and soluble leptin receptor and the bound/free ratio after pronounced weight reduction. RESEARCH METHODS AND PROCEDURES: A total of 18 morbidly obese women participated in this prospective study. Subjects were examined for fat mass, leptin, and sOB-R concentrations before and 1 year after Swedish adjustable gastric banding. RESULTS: Anthropomorphic measures displayed a significant reduction of body mass index [(42.9 +/- 5.6 to 32.9 +/- 6.0 kg/m(2) (mean +/- SD)]. Fat mass decreased from 56.3 +/- 9.0 to 33.9 +/- 12.5 kg. Plasma leptin concentration decreased from 44.6 +/- 18.0 to 20.0 +/- 13.1 ng/mL (p < 0.001), whereas the sOB-R levels increased from 11.1 +/- 3.6 to 16.6 +/- 6.0 U/mL after weight-reducing surgery. Thus, the sOB-R bound fraction of leptin increased from 7% to 33%. DISCUSSION: This work demonstrates a relationship between weight loss, leptin, and sOB-R concentrations in vivo. During weight loss, leptin levels decreased, whereas sOB-R levels and the receptor bound fraction of leptin increased. Thus, sOB-R may negatively regulate free leptin.

Adult↗

PubMed1973

Effect of alcohols and neutral salt on the thermal stability of soluble and precipitated acid-soluble collagen.

The effects of mono- and poly-hydric alcohols in the presence of KCl on the intrinsic stability of collagen molecules in dilute acid solution were compared with corresponding solvent and salt effects on the increased stability of the aggregated molecules in salt-precipitated fibrils. Salt addition decreased solubility and increased the thermal stability of fibrils, but progressively decreased the stability of collagen molecules in solution. In contrast, the alcohols enhanced solubility and decreased fibril stability, the effects increasing with solvent hydrocarbon chain length and with decreasing hydroxyl/methylene-group ratio. Molar destabilization of dissolved collagen by alcohols was lower than for fibrils, and at low salt concentration, both ethylene glycol and glycerol were structural stabilizers. Electron-micrograph studies indicated that salt-precipitated fibrils tended to adopt the native aggregation mode, and qualitatively similar solvent effects were observed in insoluble collagens. Implications of the experimental findings are discussed in terms of a model in which electrostatic and apolar interactions mainly govern the excess of stability in collagen fibrils whereas intrinsic stability of single molecules is a function of polar interactions and polypeptide-chain rigidity.

1-Propanol↗

PubMed2000

Increased serum levels of soluble vascular cell adhesion molecule-1 and soluble E-selectin in patients with polymyositis/dermatomyositis.

BACKGROUND: Elevated levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) have previously been reported in patients with various inflammatory diseases, but not in patients with polymyositis/dermatomyositis (PM/DM). OBJECTIVES: To determine serum levels and significance of sVCAM-1 and sE-selectin in patients with PM/DM. PATIENTS AND METHODS: Serum samples from 36 PM/DM patients, 30 patients with systemic sclerosis and 25 healthy control subjects were examined using specific enzyme-linked immunosorbent assay systems. RESULTS: The serum levels of sVCAM-1 in the PM/DM patients were significantly higher than those in the healthy controls. The elevated serum sVCAM-1 levels were correlated with the values of elevated erythrocyte sedimentation rate and elevated serum hyaluronate levels in the PM/DM patients. The serum sE-selectin levels in the PM/DM patients were also significantly higher than those in the healthy controls. The elevated serum sE-selectin levels were correlated with the incidence of elevated creatine kinase activities. The concentrations of serum sE-selectin were correlated with the serum tissue inhibitor of metalloproteinase-1 concentrations in the PM/DM patients (r = 0.53). CONCLUSIONS: These results suggest that serum sVCAM-1 and sE-selectin levels might be useful for detecting disease activity in patients with PM/DM.

Adolescent↗

PubMed2001

Serum levels of soluble stem cell factor and soluble KIT are elevated in patients with atopic dermatitis and correlate with the disease severity.

BACKGROUND: Mast cell infiltration in skin lesions of atopic dermatitis (AD) is considered to play an important role in the pathogenesis of the disease. The most common factor that stimulates mast cell growth, migration and differentiation is stem cell factor (SCF), and the interaction of SCF and its receptor, KIT (tyrosine kinase transmembrane receptor), appears to be the key event in the recruitment and proliferation of mast cells. OBJECTIVES: To determine whether any altered metabolism of SCF and/or KIT is present in patients with AD. METHODS: We measured serum levels of soluble SCF (sSCF) and soluble KIT (sKIT) using enzyme-linked immunosorbent assay in 54 patients with AD, five patients with erythrodermic psoriasis vulgaris and 64 healthy individuals. RESULTS: Serum levels of both peptides in AD patients were significantly higher than those in healthy individuals, whereas patients with psoriasis vulgaris did not show any difference from healthy controls. Both sSCF and sKIT levels were positively correlated with the disease severity in AD patients, and decreased after effective treatment with topical corticosteroids. Conclusion Serum levels of sSCF and sKIT may be useful indicators for evaluation of the activity and severity of AD.

Administration, Topical↗

PubMed1996

Soluble adhesion molecules in sera of patients with leprosy: levels of soluble intercellular adhesion molecule-1 (sICAM-1) rapidly decrease during multi-drug therapy.

The clinicopathological spectrum of leprosy is associated with an altered immunological reaction. The expression of adhesion molecules on endothelial cells directs the cellular traffic to sites of local skin and nerve inflammation. Soluble forms of adhesion molecules, which are released upon cytokine activation, can be detected in the circulation and may reflect ongoing tissue inflammation. We determined the serum levels of sICAM-1, sE-selectin and sL-selectin in 74 patients with leprosy (tuberculoid form, n = 23; lepromatous form, n = 36; acute leprous reaction, n = 16) and 15 healthy age- and sex-matched control donors. Patients with lepromatous leprosy had significantly higher levels of sICAM-1 (564 +/- 174 versus 450 +/- 92 versus 334 +/- 57 ng/ml) and E-selectin (90 +/- 31 versus 74 +/- 29 versus 50 +/- 10 ng/ml) than patients with tuberculoid leprosy and normal donors (P < 0.01). No differences between groups were detected for L-selectin. Patients with leprous reactions had similar high levels to lepromatous patients. Twenty lepromatous patients were re-examined after 4 weeks of therapy. A significant decrease in sICAM-1 serum levels was observed after 1 month of anti-mycobacterial treatment, which was accompanied by a reduction of mycobacteria in skin biopsies (P < 0.01). Patients with leprous reactions (n = 13) also demonstrated a drop in sICAM-1 after anti-inflammatory therapy. sE-selectin and sL-selectin serum values decreased only in lepromatous patients after therapy. It can be concluded that soluble adhesion molecules like sICAM-1 and sE-selectin are promising activity markers in patients with leprosy, which may be useful for treatment monitoring.

Adult↗

PubMed2003

Soluble HLA-DR and soluble CD95 ligand levels in pregnant women with antiphospholipid syndromes.

Antiphospholipid syndrome (APS) is a severe complication in pregnancy that can lead to fetal death in the second or third trimester. As soluble HLA-DR (sHLA-DR) molecules are reported to be implicated in the etiology of pregnancy disorders and of autoimmune diseases, we studied sHLA-DR plasma levels in pregnant women with APS (n = 14) and in women with normal pregnancy (n = 15), in women with high-risk pregnancies such as preeclampsia (PE; n = 20) and intrauterine growth retardation (IUGR; n = 10) and in fertile non-pregnant women (n = 29). The sHLA-DR levels of pregnant women were assessed during the third trimester, at labor, in the first week, and in the third month of puerperium. The results obtained were compared with soluble CD95 ligand (sCD95L), an important signal molecule in the apoptosis pathway. The sHLA-DR levels in pregnant women with APS were approximately three times higher (mean 1.48 +/- 0.15 microg/ml) during the whole observation period than in fertile non-pregnant women (0.54 +/-.06 microg/ml) and nearly double in women with high risk (PE, 0.91 +/- 14 microg/ml; IUGR, 0.94 +/-.21 microg/ml) and in normal pregnancies (0.74 +/- 0.13 microg/ml). Furthermore, sHLA-DR levels of pregnant women with APS were positively correlated with the serum concentration of anti-anticardiolipin immunoglobulin G antibodies. For sCD95L plasma levels, no substantial variations were found among the different groups above. In pregnant women with APS, however, sHLA-DR levels were positively correlated with sCD95L levels. Further studies should clarify the functional involvement of sHLA-DR molecules in the induction of CD95/CD95L-mediated apoptosis pathway that may play a crucial role in the pathology of pregnancies complicated by APS.

Adult↗

PubMed2001

Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses.

Signal transduction in response to interleukin-6 (IL-6) requires binding of the cytokine to its receptor (IL-6R) and subsequent homodimerization of the signal transducer gp130. The complex of IL-6 and soluble IL-6R (sIL-6R) triggers dimerization of gp130 and induces responses on cells that do not express membrane bound IL-6R. Naturally occurring soluble gp130 (sgp130) can be found in a ternary complex with IL-6 and sIL-6R. We created recombinant sgp130 proteins that showed binding to IL-6 in complex with sIL-6R and inhibited IL-6/sIL-6R induced proliferation of BAF/3 cells expressing gp130. Surprisingly, sgp130 proteins did not affect IL-6 stimulated proliferation of BAF/3 cells expressing gp130 and membrane bound IL-6R, indicating that sgp130 did not interfere with IL-6 bound to IL-6R on the cell surface. Additionally, sgp130 partially inhibited proliferation induced by leukemia inhibitory factor (LIF) and oncostatin M (OSM) albeit at higher concentrations. Recombinant sgp130 protein could be used to block the anti-apoptotic effect of sIL-6R on lamina propria cells from Crohn disease patients. We conclude that sgp130 is the natural inhibitor of IL-6 responses dependent on sIL-6R. Furthermore, recombinant sgp130 is expected to be a valuable therapeutic tool to specifically block disease states in which sIL-6R transsignaling responses exist, e.g. in morbus Crohn disease.

Acute-Phase Reaction↗

PubMed1997

Soluble interleukin 2 receptor and soluble CD8 levels in previously treated human immunodeficiency virus-negative hemophiliacs multiply transfused with a monoclonal antibody-purified factor VIII concentrate.

BACKGROUND: Serum levels of the soluble interleukin 2 receptor (sIL-2R) and soluble CD8 (sCD8) may be used as markers of T-cell activation. The course of serum levels of sIL-2R and sCD8 in hemophiliacs who were treated first with an intermediate-purity factor VIII concentrate and then with a monoclonal antibody (MoAb)-purified factor VIII concentrate are reported. STUDY DESIGN AND METHODS: Serum samples taken before the administration of the MoAb-purified concentrate and after 2 and 5 years of its administration to 20 human immunodeficiency virus-negative patients with hemophilia A were analyzed. Eighteen healthy age-matched men were used as controls. RESULTS: The sIL-2R and sCD8 levels were higher in patients treated with intermediate-purity concentrates than in controls (p = 0.006 and p = 0.0005, respectively). The sIL-2R levels showed a decrease after 5 years of treatment with the MoAb-purified concentrate (p = 0.018 for the difference between 2 and 5 years), to levels that were not significantly different from those in controls. Although sCD8 levels tended to decrease at 5 years (p = 0.09, for the difference between 2 and 5 years), they remained higher than those in controls (p = 0.0005 and p = 0.0016 at 2 and 5 years, respectively). The ratio of sCD8 and sIL-2R tended to increase between 2 and 5 years (p = 0.07). The sIL-2R and sCD8 levels were not related to the numbers of T-lymphocytes and HLA-DR-positive T-lymphocytes in peripheral blood. Nor was a relation demonstrated between sIL-2R levels and CD4-positive cell numbers or between sCD8 levels and CD8-positive cell numbers. Although a relation with chronic hepatitis C cannot be excluded, it seems more likely that changes in sIL-2R levels are due to the use of the MoAb-purified concentrate. CONCLUSION: Elevated levels of sIL-2R and sCD8 were found in multiply transfused human immunodeficiency virus-negative hemophiliacs. After treatment was changed to the use of a MoAb-purified concentrate. sIL-2R levels decreased. These findings suggest a change in immune stimulation that is remarkable, because signs of activation in the effector phase seem to have continued despite normalization in the proliferative phase.

Adult↗

PubMed2000

Soluble Fas and soluble Fas-ligand in children with Escherichia coli O157:H7-associated hemolytic uremic syndrome.

We measured soluble Fas-ligand (sFas-L) and soluble Fas (sFas) levels by sandwich enzyme-linked immunosorbeny assay and compared them among (1) healthy controls (n = 11), (2) children with hemorrhagic colitis (HC) caused by a non-verotoxin-producing pathogen (n = 23), (3) patients with uncomplicated Escherichia coli O157:H7 HC (n = 14), and (4) children with O157:H7-associated hemolytic uremic syndrome (HUS) (n = 24). Children with uncomplicated E coli O157:H7 HC and HUS were matched for duration of enteric prodrome before blood sample collection. We also compared sFas-L and sFas levels among patients with HUS according to severity of renal dysfunction; abnormally increased sFas-L levels were noted in only 4% of the children (n = 3). Abnormally high concentrations of sFas were noted in 9% of the children with HC caused by a non-verotoxin-producing pathogen, 29% of the patients with uncomplicated E coli O157:H7 HC, and 69% of the children with O157:H7-associated HUS. Compared with healthy controls, patients with HUS had twofold greater concentrations of sFas (P: < 0.0001). Levels of sFas were not statistically different between 14 patients with uncomplicated O157:H7 HC and 14 children with HUS (8.2 +/- 4.7 versus 11.0 +/- 4.6 U/mL, respectively; P: < 0.07) when matched for time after onset of enteritis (7.0 +/- 3.7 versus 7.3 +/- 3.8 days, respectively). Greater concentrations of sFas were noted in patients with HUS who developed oligoanuria (n = 10; P: < 0.007), required peritoneal dialysis (n = 10; P: < 0.007), or had a decreased glomerular filtration rate (n = 5; P: < 0.002) 1 year later. Our data show that plasma concentrations of sFas but not sFas-L are abnormally increased in children with O157:H7 infections. Levels of sFas are associated with severity of renal dysfunction during HUS. Further studies are needed to clearly determine the role and origin of circulating sFas among children with infections caused by E coli O157:H7.

Adolescent↗

PubMed2001

Soluble Fas and soluble Fas ligand levels in patients with acute hepatic failure.

PURPOSE: The Fas ligand (FasL)/Fas system is an apoptosis induction system that plays an important role in homeostasis and biophylaxis. We measured tumor necrosis factor alpha (TNF-alpha), soluble FasL (sFasL), and soluble Fas (sFas) in patients with acute hepatic failure to determine the relation between such failure and apoptosis. MATERIALS AND METHODS: We assayed 21 blood samples from patients with acute hepatic failure and 8 from patients with sepsis but without acute hepatic failure. Serum TNF-alpha, sFas, and sFasL levels were determined by enzyme-linked immunosorbent assay. RESULTS: sFasL levels were significantly higher in the patients with acute hepatic failure than in the patients with sepsis (0.68 +/- 0.42 ng/mL vs. 0 ng/mL, P =.0001). No significant differences were observed in sFas levels between the two groups. A significant correlation was observed between TNF-alpha and sFas levels (r = 0.657, P =.0008); a negative correlation was observed between TNF-alpha and sFasL levels (r = 0.454, P =.038). CONCLUSIONS: Our results suggest that pathologic aggravation of acute hepatic failure are related to changes in the FasL/Fas system and that TNF-alpha and sFasL, in particular, may play hepatoprotective roles.

Aged↗

PubMed1996

The function of the soluble interleukin 6 (IL-6) receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL-6 and prolongation of the plasma half-life of IL-6.

Interleukin 6 (IL-6) is considered an important mediator of acute inflammatory responses. Moreover, IL-6 functions as a differentiation and growth factor of hematopoietic precursor cells, B cells, T cells, keratinocytes, neuronal cells, osteoclasts, and endothelial cells. IL-6 exhibits its action via a receptor complex consisting of a specific IL-6 receptor (IL-6R) and a signal transducing subunit (gp130). Soluble forms of both receptor components are generated by shedding and are found in patients with various diseases such as acquired immune deficiency syndrome, rheumatoid arthritis, and others. The function of the soluble (s)IL-6R in vivo is unknown. Since human (h)IL-6 acts on human and murine target cells, but murine IL-6 on murine cells only, we constructed transgenic mice expressing the hsIL-6R. We report here that in the presence of hsIL-6R, mice are hypersensitized towards hIL-6, mounting an acute phase protein gene induction at significantly lower IL-6 dosages compared to control animals. Furthermore, in hsIL-6R transgenic mice, the detected acute phase response persists for a longer period of time. The IL-6/IL-6R complex prolongs markedly the Il-6 plasma half-life. Our results reinforce the role of the hsIL-6R as an agonistic protein, help to understand the function of the hsIL-6R in vivo, and highlight the significance of the receptor in the induction of the acute phase response.

Acute-Phase Reaction↗