Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum levels of various cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL1-beta), and interleukin 2 (IL2), and of soluble IL2 receptors (sIL2R) were determined in 30 patients with definite systemic sclerosis (SSc). Spontaneous and lipopolysaccharide-or mitogen-induced production of the cytokines, TNF-alpha, IL1-beta, and IFN-gamma, by peripheral blood mononuclear cells (PBMNC) of these SSc patients was measured by immunoassays. The patients were divided into three groups: 12 with limited cutaneous disease (lcSSc), 7 with diffuse cutaneous disease (dcSSc) < 3 years duration, and 11 with dcSSc > 3 years duration. None were treated with cytotoxic drugs or biologic response modifiers. Sera of patients with SSc had elevated sIL2R levels, and only low levels of IL2 (1-2 U/ml) were detected in 10/29 sera tested. Spontaneous production of TNF-alpha and IL1-beta by PBMNC of patients with SSc (829 pg/ml +/- 215 SEM and 728 pg/ml +/- 186, respectively) was significantly higher than that by normal PBMNC obtained from 30 volunteers (25 +/- 10 and 34 +/- 6 pg/ml, respectively) and tested at the same time as patients' PBMNC. The largest increases in spontaneous release of TNF-alpha or IL1-beta were seen in patients with early dcSSc. No significant difference in spontaneous IFN-gamma production by patient or control PBMNC was detected. On the other hand, the mean level of mitogen-induced IFN-gamma production by PBMNC was significantly depressed in patients with SSc (103 U/ml +/- 18 vs 255 +/- 33 U/ml in controls). In vitro-induced production of TNF-alpha or IL1-beta by patients' PBMNC was comparable to that of normal PBMNC. These data indicate that in vivo-activated PBMNC of patients with SSc spontaneously secrete excessive amounts of fibrogenic cytokines, which are involved in modulation of connective tissue synthesis.
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PMID:Cytokine production and serum levels in systemic sclerosis. 145 30

Samples of protein from the urine of 23 patients with lupus nephropathy and 15 patients with proteinuria who did not have systemic lupus erythematosus (SLE) were studied for the presence of cytokines, soluble interleukin 2 receptors (sIL-2R), and free light chain immunoglobulins. The patients with lupus nephropathy were divided into two groups with active (nephritis) and inactive inflammation (nephrosis) based on the results of the analysis of urine samples and renal histology. The crude urine proteins (5 mg/ml) after precipitation by 80% ammonium sulphate from 14 patients with lupus nephritis contained higher concentrations of sIL-2R (4.88 (SEM 1.27 ng/ml) than those from nine patients with nephrosis (1.11 (0.52) ng/ml) or 15 patients without SLE (1.31 (0.87) ng/ml). The concentration of sIL-2R in protein from urine samples was not correlated with the concentration in plasma and was inversely correlated with the excretion of protein in urine over 24 hours in patients with SLE. It is suggested that, in addition to leakage from the circulation, the local production of sIL-2R by inflamed kidneys is possible. The crude proteins in urine were further fractionated by gel filtration on Sephacryl S-200. Arbitrarily, four fractions could be obtained from urine from patients with SLE but only three fractions were found in the urine of patients without SLE. Fraction IV derived from patients with nephritis or nephrosis augmented the pokeweed mitogen induced [3H]thymidine uptake of mononuclear cells. In addition, the positive rates of free kappa (kappa) (35.7%) and lambda (lambda) (42.9%) chains in proteins in urine from nephritic patients were higher than those in the other two groups. These results suggest that the severity of inflammation in the kidneys of patients with lupus can be reflected by the increased excretion of sIL-2R, free light chain immunoglobulins, and cytokine-like molecules in urine.
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PMID:Increased excretion of soluble interleukin 2 receptors and free light chain immunoglobulins in the urine of patients with active lupus nephritis. 155 Mar 98

To study the factors that influence cytokine release, the effect of endotoxin on in vitro tumor necrosis factor production by monocytes from debilitated patients with cancer (n = 6) was compared with that from healthy controls (n = 5). Spontaneous and endotoxin-stimulated monocyte tumor necrosis factor production was similar in patients with cancer and controls. However, with total peripheral blood mononuclear cells, enhancement of tumor necrosis factor production by endotoxin in patients with cancer (46 +/- 12, mean +/- SEM) was greater than in controls (0% +/- 7%). This enhanced response correlated with reduced peripheral blood mononuclear cell blastogenesis in response to phytohemagglutinin (r = .66) and could be partially reversed in vitro by addition of exogenous interleukin 2. Thus, a component of total peripheral blood mononuclear cells (probably T cells) seems to influence monocyte cytokine production in response to endotoxin. Moreover, this regulatory component is decreased in patients with cancer, correlates with decreased peripheral blood mononuclear cell blastogenesis, and can stimulated with interleukin 2.
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PMID:Regulation of tumor necrosis factor production in healthy humans and in patients with cancer. 159 73

To study antitumor functions of T-lymphocyte subpopulations in the blood [peripheral blood lymphocytes (PBLs)] and tumor-draining lymph nodes (LNs) of patients (n = 26) with squamous cell carcinoma of the head and neck (SCCHN), antibody-coated devices were used to positively select CD8+ or CD4+ cells. The mean percentage of CD8+ cells captured on antibody-coated flasks from PBLs was 92% and that captured from lymph node lymphocytes (LNLs) was 98%. The initial enrichment in CD4+ T-cells was comparable. CD8+ T-lymphocytes captured from PBLs proliferated as well as unseparated lymphocytes in both patients with SCCHN and normal donors, while captured CD4+ PBLs of the patients showed significantly lower expansion than those of normal volunteers. Unseparated LNLs proliferated as well as PBLs, but captured CD4+ or CD8+ LNLs failed to proliferate in the presence of interleukin 2 (100 units/ml) and phytohemagglutinin (5 micrograms/ml). The addition to captured LNL cultures of irradiated autologous or allogeneic feeder cells significantly improved expansion of CD8+ LNLs but not CD4+ LNLs. During 15-day culture of captured CD8+ PBLs or CD8+ LNLs in the presence of feeder cells, a significant (P less than 0.05) enrichment in CD8+ T-cells was maintained [94 +/- 5% (mean +/- SEM) or 99.5 +/- 0.1%, respectively, on day 15]. Capture of CD8+ LNLs and their expansion resulted in the outgrowth of CD8+CD11b- effectors which had no or little cytotoxicity against Daudi, low cytotoxicity against K562, and very high levels of cytotoxicity against 4 different natural killer cell-resistant SCCHN targets, as measured in 4-h 51Cr release assays. Such significant enrichment in SCCHN-restricted cytotoxicity could be obtained with LNLs from tumor-uninvolved LNs but not from tumor-involved LNs. Captured and cultured CD4+ LNLs had no preferential anti-SCCHN cytotoxicity. The addition of irradiated autologous tumor cells to captured CD8+ PBLs did not result in improved proliferation or antitumor function of the effector cells. Positive selection on antibody-coated flasks of CD8+ T-lymphocytes from tumor-uninvolved LNs of patients with SCCHN led to the enrichment in SCCHN-restricted but the major histocompatibility complex-unrestricted effector cells in 15-day cultures. Thus, CD8+ lymphocytes separated from tumor-draining LNs in patients with head and neck cancer contained cytolytic T-cell precursors capable of developing into effectors with preferential activity against SCCHN targets.
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PMID:Enrichment in tumor-reactive CD8+ T-lymphocytes by positive selection from the blood and lymph nodes of patients with head and neck cancer. 167 10

Long-term specific tolerance to one haplotype class I plus minor antigen disparate renal allografts develops without exogenous immunosuppression in approximately 35% of miniature swine (n = 128). Previous studies have suggested that this phenomenon is related to limited class I-specific helper T cell activity as evidenced by the failure of antibody class switching in vivo and the ability of exogenous interleukin 2 to elicit antidonor responses in vitro. To determine whether tolerance could be broken by inducing antidonor reactivity with donor antigen and a source of T cell help, multiple skin grafts bearing donor class I plus third-party class II antigens were placed on tolerant animals. Skin grafts were placed at least 3 months after the kidney transplant, at which time all recipients had normal renal function as measured by blood urea nitrogen and serum creatinine. First-set rejection of skin grafts by SLAad and SLAdd hosts occurred in 11.8 +/- 1.1 days (mean +/- SEM, n = 6) and in 9.3 +/- 0.9 days (n = 4), respectively. Coincident with skin rejection, most animals developed a transient rise in BUN to 62 +/- 11 mg/dl (n = 10) and a similar rise in Cr to 4.9 +/- 1.2 mg/dl (n = 10), with normal levels returning in all animals within two weeks. Subsequent skin grafts with the same disparity did not undergo second-set rejection and did not induce BUN or Cr elevations. Prior to skin grafting, animals showed no antidonor activity in mixed lymphocyte reaction or cell-mediated lymphocytotoxicity assays. After two skin grafts, all animals developed donor-specific CML and secondary MLR responses, and additional skin grafts amplified this cellular immunity. Development of marked antidonor immunity without a break in tolerance suggested that either graft adaptation or local suppression might be involved in maintaining tolerance to class I MHC antigens. In preliminary studies, an immunized SLAad animal and an immunized SLAdd animal were retransplanted with kidneys MHC matched to their first allografts. In both cases, the second graft was accepted permanently without immunosuppression, suggesting that graft adaptation is not necessary for the maintenance of tolerance to renal allografts in miniature swine.
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PMID:The failure of skin grafting to break tolerance to class I-disparate renal allografts in miniature swine despite inducing marked antidonor cellular immunity. 175 67

Anticardiolipin antibodies purified from serum from patients with systemic lupus erythematosus (SLE) by cardiolipin micelles were studied for their effects on lymphocytes and neutrophils. At a concentration of 160 micrograms/ml they markedly suppressed the [3H]thymidine incorporation of mononuclear cells stimulated by phytohaemagglutinin (4.9 (SEM 1.9%) of the control) and pokeweed mitogen (26.7 (10.5%) of the control). In addition, anticardiolipin antibodies changed the cell cycle of phytohaemagglutinin stimulated lymphocytes such that the S and G2+M phases were significantly diminished (G0/G1 = 64.62%, S = 20.59%, G2+M = 14.78% in the presence of normal human IgG v G0/G1 = 86.07%, S = 10.32%, G2+M = 3.59% in the presence of anticardiolipin antibodies). The suppression of lymphocyte proliferation by anticardiolipin antibodies was shown not to be caused by an alteration of T cell subpopulations. However, the interleukin 2 receptors on the cell surface and the soluble interleukin 2 receptors in the supernatant of phytohaemagglutinin stimulated mononuclear cells were decreased in the presence of anticardiolipin antibodies. On the other hand, the phagocytic activity of neutrophils was 40% inhibited at a higher concentration of anticardiolipin antibodies (300 micrograms/ml) through suppression of C3b/C4b and Fc receptors on polymorphonuclear leucocytes. These results suggest that anticardiolipin antibodies exert inhibitory effects on both lymphocytes and phagocytes in addition to the coagulation cascade. These newly found activities of anticardiolipin antibodies were mediated by the non-specific membranotropic property of the antibodies.
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PMID:Inhibitory effects of anticardiolipin antibodies on lymphocyte proliferation and neutrophil phagocytosis. 176 56

We recently reported evidence for the involvement of local cellular immune activation in the immunopathogenesis of human IgA nephropathy, particularly in cases of IgA disease featuring crescent formation. In the current study, using monoclonal antibodies, we investigated whether mononuclear cells bearing receptors for interleukin 2 (IL-2R+ MNC) were present within glomeruli or associated crescents in biopsies from patients with crescentic glomerulonephritis (greater than 60% crescents, N = 19), IgA disease with crescents (N = 9), or other types of proliferative glomerulonephritis with crescents (10 to 44%, N = 6), compared with normal control kidneys (N = 10). Biopsies were further classified into those showing active (cells, fibrin) (N = 15) or inactive (sclerosed) crescents (N = 19), to determine whether IL-2R+ MNC were particularly associated with active crescent formation. Few leucocytes were found within glomerular tufts of normal kidneys (2.4 +/- 0.7 cells/glomerular cross-section; mean +/- SEM). By contrast, in biopsies from patients with active crescentic glomerulonephritis, total intraglomerular tuft leucocytes were increased to 14.0 +/- 1.7 (P less than 0.01 vs. normal kidneys), largely due to increased numbers of intraglomerular monocytes (10.4 +/- 1.1, P less than 0.01) and T cells (3.7 +/- 0.6, P less than 0.01). Biopsies with active crescents also contained significantly increased numbers of intraglomerular tuft IL-2R+ MNC (4.0 +/- 0.7, 29% of total intraglomerular leucocytes), and there was a strong correlation between the numbers of intraglomerular IL-2R+ MNC and T cells (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activated (IL-2R+) intraglomerular mononuclear cells in crescentic glomerulonephritis. 205 38

Children with uncontrolled autoimmune chronic active hepatitis have increased numbers of activated T lymphocytes expressing interleukin 2 receptors (IL2R). A soluble form of IL2R has recently been described whose proposed role is to downregulate T cell activation by competing for interleukin 2. We investigated whether a deficiency of soluble IL2R could account for the high concentrations of IL2R positive T lymphocytes in autoimmune chronic active hepatitis. Soluble IL2R was measured by enzyme-linked immunosorbent assay in the serum of 16 children with autoimmune chronic active hepatitis, eight with chronic liver disease due to hepatitis B virus infection, seven with Wilson's disease, nine with alpha 1 antitrypsin deficiency, and 15 healthy age matched controls. Soluble IL2R concentration was significantly higher in patients with autoimmune chronic active hepatitis than in healthy controls (mean (SEM) 475 (75) U/ml, 145 (8) U/ml respectively, p less than 0.01). Eleven patients who had active disease had significantly higher soluble IL2R concentrations (590 (89) U/ml) than the five cases with inactive disease (220 (36) U/ml, p less than 0.01). No difference was found between the controls and the patients with chronic liver disease due to hepatitis B infection, Wilson's disease, and alpha 1 antitrypsin deficiency. Percentages and absolute numbers of surface IL2R positive T cells as detected by immunofluorescence were significantly higher in the patients with autoimmune chronic active hepatitis (11.8% (1); 274/microliters (31)) than in controls (0.2% (0.1); 5/microliters (2), p less than 0.001), the highest values being found in those with uncontrolled disease. A significantly positive correlation was observed between concentrations of soluble IL2R and the percentage of T cells expressing IL2 receptors (r=0.67, p<0.001). These results indicate that the high levels of IL2R positive T lymphocytes characteristic of autoimmune chronic active hepatitis are not due to a deficiency of soluble IL2 receptors.
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PMID:Soluble interleukin 2 receptors in autoimmune chronic active hepatitis. 237 74

Accumulating evidence suggests a link between immediate hypersensitivity and cellular immunity. In this study, we examined the effect of interleukin 2 (IL-2) on basophil histamine release. Histamine-releasing activity of IL-2 was very weak with % histamine release of 2.9 +/- 1.3 (mean +/- SEM, n = 9) at 1:12 dilution. IL-2 at 1:1200 dilution slightly inhibited anti-IgE-induced histamine release by 22.4 +/- 18.6% (P greater than 0.05). There was a significant potentiation of release at 1:12 dilution of IL-2 with % enhancement of 78.7 +/- 42.2 (P less than 0.05). IL-2 enhanced the calcium ionophore A23187-induced histamine release in a dose-dependent fashion. IL-2 at 1:12 dilution significantly potentiated release by 28.8 +/- 6.3% (P less than 0.05). There was a slight suppression of formyl-methionyl-leucyl-phenylalanine (FMLP)-induced histamine release at 1:1200 dilution with % inhibition of 23.4 +/- 7.4 (P greater than 0.05). At 1:12 dilution, IL-2 significantly potentiated FMLP-induced release by 73.7 +/- 41.6% (P less than 0.05). Recombinant IL-2 (RIL-2) augmented anti-IgE-induced histamine release with a significant enhancement at 200 units/ml. Conventional IL-2 was more potent than RIL-2 in enhancing release. These results indicate that IL-2 enhances basophil histamine release and some part of the effect of IL-2 on basophils is derived from other factors contained in conventional IL-2.
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PMID:Effect of interleukin 2 on basophil histamine release. 243 59

The administration of interleukin 2 (IL-2) to mice and humans is limited by the induction of a dose-dependent increase in vascular permeability causing a vascular leak syndrome (VLS). We have investigated the impact of the injection of recombinant interleukin 1 alpha (IL-1 alpha) on the VLS induced by IL-2 by measuring the extravasation of 125I-albumin into tissues and by assessing wet and dry lung weights. IL-1 alpha alone did not induce any significant extravasation of radiolabeled albumin. IL-2 alone, however, caused a significant increase in the extravasation compared to control lungs. IL-1 alpha injection along with IL-2 significantly reduced the IL-2-induced extravasation of radiolabeled albumin [9,886 +/- 533 (SEM) cpm were observed in IL-2 and IL-1 alpha-treated lungs compared to 14,172 +/- 2,628 cpm in lungs treated with IL-2 alone (P less than 0.02)]. IFN-alpha in combination with IL-2 produced more severe vascular leakage than caused by IL-2 alone. IL-1 alpha also significantly decreased (P less than 0.05) the vascular permeability induced by the combination of IFN-alpha and IL-2. We observed 44,811 +/- 13,131 cpm in IFN-alpha- and IL-2-treated lungs compared to 18,350 +/- 2,622 cpm in IFN-alpha-, IL-2-, and IL-1 alpha-treated lungs. The IL-2- and IFN-alpha-induced increase in lung water weight was also reduced significantly by the addition of IL-1 alpha. The decrease in vascular leakage was dependent on the dose and timing of IL-1 alpha administered. When recombinant IL-1 alpha was given as a single i.p. injection, 24 h before the injection of IL-2 (or Hanks' balanced salt solution) or IL-2 and IFN-alpha no abrogation of the VLS was observed. Although IL-1 alpha decreased VLS significantly in mice treated with IFN-alpha and IL-2 the survival of mice was not improved by the simultaneous administration of IL-1 alpha. Histologically, treatment with IFN-alpha and IL-2 produced marked perivascular and intraalveolar edema which was completely eliminated by the addition of IL-1 alpha. However, some perivascular edema in IL-1 alpha-treated mice remained which was equivalent to that caused by IL-2 alone. Treatment of MCA-106 induced pulmonary metastases was enhanced by the administration of IFN-alpha and IL-2 together.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Decrease in interleukin 2-induced vascular leakage in the lungs of mice by administration of recombinant interleukin 1 alpha in vivo. 278 61


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