Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several previous studies have demonstrated increased in vivo release of soluble interleukin-2 receptors (sIL-2R) in patients with disorders associated with cellular activation. In this study attempting to understand better the role of sIL-2R released in vivo, we investigated the sIL-2R levels in paired serum and urine samples from 25 patients with systemic lupus erythematosus (SLE), 41 patients with rheumatoid arthritis (RA) and 20 healthy subjects. Using an ELISA for sIL-2R, we detected significantly increased urinary sIL-2R levels in normal individuals (868 +/- 114 units/ml) compared to the corresponding serum samples (209 +/- 25, P < 0.001, mean urine/serum sIL-2R ratio: 4.5 +/- 0.6), which suggests that the clearance of sIL-2R from circulation is largely kidney-dependent. The patients with SLE and RA exhibited significantly increased serum sIL-2R levels compared to normals (682 +/- 115 and 734 +/- 101 units/ml, respectively, P < 0.001) and these levels correlated with disease activity. However, urinary excretion of sIL-2R in these patients (SLE: 620 +/- 154 units/ml; RA: 1084 +/- 148 units/ml) was found to be significantly decreased (mean urine/serum sIL-2R ratio in SLE: 0.9 +/- 0.2; in RA: 1.9 +/- 0.2; P < 0.001) compared to normals, possibly contributing to the accumulation of these soluble receptors in the serum of autoimmune patients after their release from cells. Our findings can be attributed either to the binding of the sIL-2R to serum protein(s) or to distinct structural features of serum sIL-2R in SLE and RA patients, interfering with the urinary excretion of these molecules.
Lupus 1992 Feb
PMID:Impaired urinary excretion of soluble IL-2 receptors in patients with systemic lupus erythematosus and rheumatoid arthritis. 130 61

Interferon-gamma activates both in vitro and in vivo macrophage functions. Injection of rat recombinant interferon-gamma (rR-IFN-gamma) induced the expression of interleukin-2 receptors (IL-2R) by peritoneal macrophages from normal BALB/c and MRL-+/+ mice. Moreover, rR-IFN-gamma stimulated in a dose-dependent manner the oxidative burst of cells as revealed by luminol-dependent chemiluminescene (LDCL). Resident peritoneal macrophages from MRL-lpr/lpr (mice that develop a systemic lupus-like syndrome) showed a higher PMA-triggered LDCL response. This enhanced activity was accompanied by an increase in IL-2R expression (30% vs. less than 1%). The "activated" macrophages from rR-IFN-gamma-treated normal mice as well as MRL-lpr/lpr mice did not respond to the addition of recombinant interleukin-2 (rHu-IL-2) by an increase in LDCL. However, rHu-IL-2 triggering became efficient when cells enriched in IL-2R-bearing macrophages were preincubated overnight with rHu-IL-2R. This response may point out a functional role for IL-2R and provide a role for IL-2 in certain macrophage functions.
 ...
PMID:Role of interferon-gamma on the in vivo expression of functional interleukin-2 receptors by murine macrophages. 193 95

Different characteristics of peritoneal macrophages have been studied, to assess the role of macrophages in the pathogenesis of MRL-lpr/lpr mice which develop a lupus-like syndrome. Resident peritoneal macrophages from MRL-lpr/lpr mice (greater than 10 weeks old) displayed characteristics of activation, while thioglycollate-elicited or resident macrophages from normal mice (Balb/c or MRL-+/+) did not. In addition to Ia antigens, macrophages spontaneously expressed Interleukin-2 receptors (IL2-R) whereas resident macrophages from normal mice did not. Injection of recombinant human Interleukin-2 (rHu-IL2) by the i.p. route to normal mice did not modify the cellular composition of the resident peritoneal population. On the contrary, rHu-IL2 treatment of MRL-lpr/lpr mice induced an enhancement in cell number in the peritoneal cavity. At the same time, macrophages harvested from treated MRL-lpr/lpr mice showed enhanced chemiluminescence triggered by phorbol-12-myristate-13-acetate (PMA) whereas peritoneal macrophages from treated normal mice did not. These results indicate that MRL-lpr/lpr peritoneal macrophages display features of selective 'activation' and suggest that the expression of IL2-R could be involved in the pathogenesis of inflammatory disorders seen in MRL-lpr/lpr autoimmunity.
 ...
PMID:Effect of in vivo injection of recombinant human interleukin-2 on peritoneal macrophages from MRL-lpr/lpr mice. 307 62

Attempts to detect immune mediators in RA synovial fluids by bioassay or radioimmunoassay have yielded conflicting results, and so we have begun to analyse the complex immunological reactions occurring within the rheumatoid joint using recombinant DNA technology. High levels of Interleukin-2 (IL-2) and IL-2 receptor transcripts were found in the mononuclear cells of the rheumatoid lesions. Interferon gamma (IFN gamma) mRNA was also detected, although at lower level than IL-2. To investigate the possible relevance of IL-2 and IL-2 receptor mRNA expression to the chronicity of the disease, RA joint cells were cultured in the absence of any stimulus, and the duration of mRNA expression compared to that of blood mononuclear cells (PBM), optimally stimulated. IL-2 mRNA was found to persist in culture for many days, in contrast to its transient (less than 24 h) presence in stimulated PBM. IL-2 receptor expression was also prolonged. In contrast IFN gamma mRNA, present at biopsy in 10/12 RA samples, was found to increase significantly in vitro. These results suggest that persistent T cell activation is of importance in the pathogenesis of RA, and suggests that prolonged mediator production (IL-2 and IFN gamma) may be of importance. The elevation of IFN gamma mRNA in culture and its lower relative expression suggests that there are inhibitory immunoregulatory influences within the RA joint. To determine whether abnormal IL-2 mRNA expression may be due to a genetic defect in the region controlling IL-2 gene expression, Southern blotting analysis of genomic DNA was performed with a 5' flanking probe using normal, RA and systemic lupus erythematosis patients. No abnormalities were detected.
 ...
PMID:Detection of activated T cell products in the rheumatoid joint using cDNA probes to Interleukin-2 (IL-2) IL-2 receptor and IFN-gamma. 312 92

Levels of interleukin-2 receptors (IL-2R), as measured by a double-antibody "sandwich" enzyme-linked immunosorbent assay technique, were markedly elevated in the serum of patients with systemic lupus erythematosus, rheumatoid arthritis, and bacterial endocarditis, but not in patients with acute gout. Serum levels of IL-2R correlated strongly with clinical and laboratory indicators of disease activity in patients with lupus and in those with rheumatoid arthritis. This relationship was confirmed by sequential determinations in individual patients. Serum IL-2R values correlated with disease activity better than did the Westergren erythrocyte sedimentation rate. Our findings indicate that serum levels of IL-2R may serve as a reliable serologic indicator of disease activity in inflammatory diseases characterized by immune system activation.
 ...
PMID:Serum levels of interleukin-2 receptor and activity of rheumatic diseases characterized by immune system activation. 326 65

MRL/Mp-lpr/lpr (MRL/l) mice are widely known as poor inducers of interleukin-2 (IL-2) and low responders to IL-2. It was reconfirmed that the spleen cells of MRL/l mice induced a small amount of IL-2 in vitro. In vivo experiments revealed that recombinant IL-2 (rIL-2) affected T cell subpopulations in MRL/l mice. rIL-2 decreased the numbers of Thy-1 and Lyt-1 positive cells and increased those of Lyt-23, Lyt-123 and Lyt-null cells in the thymus. It decreased the number of T cell subpopulations in the lymph nodes and spleen. These data disclosed that IL-2 might affect not only the development of T cells but also the movement of T cells among the immune organs. Some synthetic immunomodulators augmented and others suppressed or had no effect on IL-2 induction activity in the spleen of MRL/l mice. There was no correlation between the clinical efficacy of drugs on rheumatic disease and experimental IL-2 induction activity. rIL-2 and human peripheral T cell derived IL-2 (hIL-2) produced similar results in short term therapeutic experiments. When rIL-2 (1,000 U/mouse) or hIL-2 (equivalent dose) was given to MRL/l mice intraperitoneally, once a week, from 8 to 16 weeks of age, anti-double stranded DNA (dsDNA) antibody and anti-single stranded DNA (ssDNA) antibody titers had no changes. IL-2 had no effect on the renal lesions histopathologically. IL-2 induction activity was also assayed using spleen cells of the animals at the time of necropsy. The results showed that the mice treated with IL-2 had lower IL-2 induction activity than nontreated MRL/l mice. mice, an animal model for systemic lupus
 ...
PMID:Interleukin-2 induction, response and therapy on murine lupus lesions in the MRL/l strain. 349 9

Interleukin-2 (IL-2) production by cells from children with various forms of arthritis, systemic lupus erythematosus, and cystic fibrosis was compared. In all cases more IL-2 was detectable at 24 than at 48 h and production was increased by addition of indomethacin. Cultures from children with either active lupus or the pneumonia of cystic fibrosis produced very little IL-2, but cultures from children with arthritis produced apparently normal amounts. We conclude that depressed production of IL-2 in juvenile arthritis may be a secondary epiphenomenon and not a primary immunologic deficit.
 ...
PMID:Interleukin-2 production by lymphocytes from blood of children with arthritis is less suppressed than in systemic lupus or cystic fibrosis. 349 11

Interleukin-2 (IL-2) deficiency is a common feature of autoimmune disease in several inbred strains of mice genetically predisposed to a lupus-like illness, including four (MRL, C57Bl/6, AKR/J, and C3H/He) bearing the lpr gene. Defective production of IL-2 in response to concanavalin A can occur even when the proliferative response to mitogens is preserved. In C56Bl/6-lpr mice there is no apparent influence of the lpr gene and IL-2 deficiency on the induction of the experimental autoimmune myasthenia gravis that follows immunization with the acetylcholine receptor. The production of IL-2 by peripheral blood mononuclear cells stimulated with PHA is decreased in patients with systemic lupus erythematosus and rheumatoid arthritis.
 ...
PMID:Interleukin-2 and autoimmune disease. 640 37

Most immunologically-mediated diseases are inflammatory in nature, as assessed by cellular infiltrates at the lesion site. Recent immunohistological studies using monoclonal antibodies on tissue sections and synovial or cerebrospinal fluid reveal that B- and T-lymphocytes (predominantly T) participate in this reaction, together with monocytes and macrophages. The etiopathogenesis of inflammatory diseases of immunological origin can be discussed at two levels. (1) Lesions may be secondary to the cytopathic effect of antibodies, either by direct cytolysis or by opsonization, antigenic modulation, or blockage of functionally-relevant molecules. Immune complexes formed in the circulation or locally at the lesion site may intervene. Direct cellular mechanisms are probably involved, as suggested by evidence in hepatitis (indirect) and in juvenile insulin-dependent diabetes (direct). K-cells may act by antibody-dependent cytotoxicity, particularly in autoimmune diabetes and thyroiditis where lymphocyte-dependent antibodies are demonstrated. Unfortunately, the absence of adequate markers does not permit adequate detection of K-cells in inflammatory reaction sites. (2) Etiological factors are multiple in a given disease and even in a single patient. Deficiency of suppressor T-cells, assessed using monoclonal anti T-cell antibodies, represents a major predisposing factor, although suppressor cell deficit may be restricted to some antigens (EBV) in certain patients. The deficiency of interleukin-2 production in lupus and rheumatoid arthritis is intriguing but the mechanism and its relationship to disease etiology are unknown. Other immunological factors include intrinsic B-cell hyperactivity, anti-T-cell auto-antibodies, and complement deficiencies, whereas non-immunological factors such as viruses, drugs or sex hormones are important but ill-defined.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The immunological basis of inflammatory diseases. 648 71

Forty-five patients with de novo acute myeloid leukemia (AML) and 22 patients with newly-diagnosed non-Hodgkin lymphoma (NHL) were investigated. Tests for antiphospholipid antibodies (APA) included the measurement of anticardiolipin antibodies (aCL) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Fifteen patients with AML (33.3%) and 9 patients with non-Hodgkin lymphoma (40.9%) presented elevated APA at diagnosis, as compared to 3 out of 174 persons of the control group (p < 0.0001). APA titles became normal in all patients responding to treatment, whereas non-responders retained elevated levels. In addition, 2 patients (1 with AML and 1 with NHL) who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or aCL positivity. At presentation, the mean levels of IgG- and IgM-aCL in patients were not significantly different from controls, and concordance between aCL and LA results reached just 12%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and soluble form of the receptor for interleukin-2 (sIL-2r) in NHL were found significantly elevated compared to controls (p < 0.001, p = 0.011 and p = 0.016 respectively). In addition, the levels of these cytokines correlated with IgG-aCL at the different times of laboratory investigations. These results demonstrate that APA may have a role as markers of disease activity and progression in some haematological malignancies.
 ...
PMID:[Antiphospholipid antibodies: their prevalence, clinical significance and correlation with cytokine levels in acute myeloid leukemia and non-Hodgkin's lymphoma]. 775 73


1 2 3 4 Next >>