Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined 55 SLE patients. By the treatment the patients entered 5 groups: groups I and II received gammaferon plus reaferon, groups III and IV received IFN plus cyclophosphamide and control group V received placvenil. Compared to controls, the best results were obtained in patients on gammaferon combined with cyclophosphamide. IFN preparations alone showed less pronounced effects. No changes were registered in the control group. We believe that IFN preparations demonstrated efficacy against SLE.
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PMID:[The use of interferon in treating systemic lupus erythematosus]. 790 44

The immune system is regulated by soluble glycoproteins produced by a wide variety of cells. IL-10 is a soluble protein produced by helper T (Th) cells, macrophages (M phi)/monocytes (Mo), and B cells, which exhibits a wide array of both immunosuppressive and immunostimulatory properties. We examined the pathological significance of this new cytokine "IL-10", and its clinical implications. IL-10 was discovered in 1989 as an activity produced by murine type 2Th (Th2) cells which suppressed cytokine production such as interferon gamma (IFN gamma) by type 1Th (Th1) cells. Its inhibitory effects were mainly recognized in vivo in animal experiments. In humans, unlike in mice, it is difficult to separate Th1 from Th2 cells. However, as we expected, marked suppressive activities on M phi/Mo were observed in humans. We have examined the serum levels of IL-10 in several diseases. In autoimmune diseases, some of the patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) had higher titers of IL-10 in their sera than the normal controls. Conversely, some patients with common variable immunodeficiency and with inflammatory bowel diseases showed lower titers of IL-10 in their sera than the healthy controls. Most bacterial endotoxin shock patients had lower levels of serum IL-10 than cardiogenic shock patients. Collectively, the ability of IL-10 to suppress the production of inflammatory monokines and to elevate anti-inflammatory monokines, suggests a strong anti-inflammatory role in diseases such as septic endotoxin shock and inflammatory bowel diseases. Also, the IL-10 antagonist such as soluble IL-10 receptor might be a candidate for the treatment of B cell mediated autoimmune diseases such as SLE by selectively enhancing Th1 immunity.
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PMID:[Clinical implication of IL-10 in patients with immune and inflammatory diseases]. 793 21

This report describes T cell lines derived from a patient with subacute cutaneous lupus after treatment with intravenous pulse cyclophosphamide. We selected for mitotically active, hypoxanthine-guanine phosphoribosyltransferase-deficient (HPRT-) T cells, by culture in a selective medium containing 6-thioguanine. When HPRT- cell lines were derived 6 days after pulse cyclophosphamide (CYC) treatment, they were predominantly CD8+ and T cell receptor (TCR) gamma/delta+, producing interferon-gamma (IFN gamma). Cell lines derived 21 days after CYC treatment were CD4+, TCR alpha/beta+ and produced both IFN gamma and interleukin-4. These results support a possible role for gamma/delta+ T cells in subacute cutaneous lupus and suggest a mechanism for the therapeutic effect of CYC.
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PMID:Characteristics of HPRT-mutant T cell lines in a lupus patient treated with cyclophosphamide. 794 81

Despite an extensive literature dealing with IL2-induced cytolytic activity, noncytotoxicity-related effects of IL2 on peripheral blood mononuclear cells (PBMC) or T cell function have received less attention. We have focused on the effects of irradiated, IL2-activated PBMC (PBMC*rIL2) on anti-CD3- and formalin-fixed heat-killed Staphylococcus aureus-induced polyclonal B cell differentiation in secondary cultures. PBMC*rIL2 act directly on B cells and cross major histocompatibility complex barriers to augment polyclonal B cell differentiation as measured by plaque-forming cell (PFC) generation. These effects are preferentially mediated by T (both CD4+ and CD8+) cells, and physical contact between effector PBMC*rIL2 and target B cells is not absolutely required for enhanced PFC generation. PBMC*rIL2 must be present for the initial 24 hr of the secondary cultures, indicating that some soluble B cell differentiation factor rapidly released by PBMC*rIL2 mediates the PFC-enhancing effect. Of IL2, IL4, IL5, IL6, IL10, IFN-gamma, and TNF-alpha, only IFN-gamma mRNA is appreciably and reproducibly increased in irradiated, IL2-activated T cells (T cells*rIL2). Nevertheless, exogenous rIFN-gamma cannot mimic and anti-IFN antibodies cannot block the PFC-enhancing effects of T cells*rIL2, indicating that some unidentified soluble factor(s) apart from or in addition to IFN-gamma is involved. IL2-induced effects on T cell noncytolytic function may help explain certain observed immune anomalies in IL2-treated patients, and a better understanding of the IL2-induced effects on T cell noncytolytic function may have ramifications for autoimmune diseases such as SLE.
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PMID:Enhancing effects of interleukin 2-treated peripheral blood mononuclear cells on subsequent B cell differentiation. 806 23

Cytokines are important protein mediators in inflammatory joint diseases. The synovial fluid and plasma concentrations of interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha), interferon-alpha (IF-alpha) and interferon-gamma (IF-gamma) were measured by RIA and ELISA in 28 rheumatoid arthritis (RA) patients (5 males and 23 females). Ten patients with knee effusions due to other causes (osteoarthritis, psoriasis, gout, rheumatic fever, systemic lupus erythematosus) were also studied. Eight of the RA patients had erosive disease. The synovial fluid IL-1 alpha and IL-2 concentrations were higher in Group 1 (erosive) [IL-1 alpha: 524 pg/ml (SEM: 127), IL-2: 3.28 ng/ml (SEM: 1.0)] than in either Group 2 (non-erosive) [IL-1 alpha: 241 pg/ml (SEM: 24), IL-2: 1.93 ng/ml (SEM: 0.6)] or Group 3 (non-RA) [IL-1 alpha: 267 pg/ml (SEM: 58), IL-2: 0.35 ng/ml (SEM: 0.6)] (p < 0.003 and p < 0.06 respectively). Plasma IL-1 and IL-2 levels were higher in Group 1 [IL-1 alpha: 408 pg/ml (SEM: 107), IL-2: 4.20 ng/ml (SEM: 1.5)] than in Group 2 [IL-1 alpha 150 pg/ml (SEM: 15), IL-2: 2.58 ng/ml (SEM: 0.7)] or Group 3 [IL-1 alpha: 140 pg/ml (SEM: 11), IL-2: 1.93 ng/ml (SEM: 0.3)] (p < 0.01, p < 0.009 respectively). There were no differences in the IFN-alpha, IFN-gamma or TNF-alpha levels between groups. These findings suggest that plasma cytokines levels may reflect synovial levels and that IL-1 alpha may play a significant role in erosive joint disease.
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PMID:Cytokine concentrations in the synovial fluid and plasma of rheumatoid arthritis patients: correlation with bony erosions. 816 43

Patients treated with natural human interferon alpha develop anti-interferon antibodies (IFN-AB) only in very rare cases. By contrast, patients with autoimmune disorders are able to generate high-titered IFN-AB against endogenous interferon alpha. One explanation for the development of auto-IFN-AB could be cross-reactivity with typical autoimmune antigens. We investigated the cross-reactivity of 3 high-titered IgG IFN-AB of female autoimmune patients (aged 32, 36, 74 years; two severe cases of SLE, one case of autoimmune thyroiditis) as well as 25 low-titered natural IgM IFN-AB of healthy blood donors (aged 19-48 years). Typical autoimmune antigens including dsDNA, ENA, as well as natural interferon beta and recombinant interferon gamma are not able to inhibit binding of IFN-AB to interferon alpha in an ELISA test system. Preincubation of sera containing either dsDNA antibodies (dsDNA-AB) (24 patients), thyroid peroxidase (TPO-AB) (9 patients) or thyroglobulin (TG-AB) (12 patients) with interferon alpha resulted in no change in the respective autoantibody titer. These data suggest that there is no cross-reactivity between IFN-alpha-AB and dsDNA-AB, TPO-AB or TG-AB. Thus, an explanation for the occurrence of IFN-AB in autoimmune disorders cannot be found in a cross-reaction between interferon alpha with typical autoimmune antigens.
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PMID:[Interferon alpha antibodies show no cross reactions with typical autoantibodies]. 834 95

T lymphocytes from subjects with active systemic lupus erythematosus (SLE) exhibit reduced cAMP-inducible, protein kinase A (PKA)-dependent phosphorylation of several intracellular substrates compared with healthy and disease controls. To ascertain whether the persistent T cell activation observed during active SLE can result in impaired PKA-dependent protein phosphorylation, normal T cells were activated in vitro by monoclonal anti-CD3-epsilon antibody and recombinant IL1-alpha (rIL1-alpha) for 24 hr. T cell activation, verified by IL2 mRNA, IL2 receptor-alpha (IL2R-alpha) mRNA, and IL2R-beta mRNA expression, did not diminish cAMP-inducible, PKA-dependent protein phosphorylation. We also tested the hypothesis that circulating factors present in active SLE serum can decrease cAMP-inducible total PKA phosphotransferase activity and PKA-dependent protein phosphorylation in normal T lymphocytes. T cells cultured for 24 hr in medium supplemented with 10% active SLE sera (from subjects who exhibited the defect of PKA-dependent protein phosphorylation) exhibited similar total PKA phosphotransferase activity and substrate phosphorylation as cells cultured in normal AB serum. Moreover, the addition of interferon-alpha (IFN-alpha) and/or immune complexes (IC) did not diminish either total PKA activity or PKA-dependent substrate phosphorylation. Lastly, we found that the defect of PKA-dependent protein phosphorylation in active SLE T cells could not be reversed by culturing the cells in culture medium supplemented with 10% AB serum for 24 hr. In conclusion, (a) deficient cAMP-inducible, PKA-dependent phosphorylation in SLE T cells is not reversible by culturing cells in vitro; (b) there is no evidence to support the concept that serum factors, including IC and IFN-alpha, can induce a defect of PKA-dependent protein phosphorylation in normal T cells.
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PMID:The effect of circulating serum factors from patients with systemic lupus erythematosus on protein kinase A (PKA) activity and PKA-dependent protein phosphorylation in T lymphocytes. 838 27

Systemic lupus erythematosus (SLE) is an autoimmune disease with a clear imbalance in the network made up of different cytokines. However this statement has been derived from studies which have focused on the analysis of some specific cytokines and few have simultaneously analyzed those cytokines that could be involved in the pathogenesis of SLE. Therefore, we decided to analyze interleukin IL-1b, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor-a (TNF-a) and gamma interferon (IFN-g) gene expression in peripheral blood mononuclear cells from 17 women with SLE and 10 normal females by a coupled reverse transcriptase-polymerase chain reaction technique. High gene expression of IL-4, IL-6, IL-10 and TNF-a was found in SLE patients as compared to normal subjects. The expression of IL-1b, IL-2 and IFN-g genes was low or undetectable. The resulting high level of cytokines with strong effect on proliferation and differentiation of B lymphocytes in SLE could be responsible for the characteristic B cell hyperactivity and autoantibody production seen in SLE.
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PMID:High levels of TH2 cytokine gene expression in systemic lupus erythematosus. 852 28

Fluorescence flow cytometry and indirect immunofluorescence were used to detect circulating IgG antiendothelial cell antibodies (IgG-AECA) in the sera of patients suffering from rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS). Pretreatment of endothelial cells with tumour necrosis factor alpha (TNF alpha), but not with interferon gamma (IFN gamma), increased the IgG binding from sera of some patients with active SLE. In contrast, no change in binding activity to cytokine-stimulated endothelial cells was observed in the RA and PSS sera. The results of this study suggested that the enhanced binding of IgG from the sera of patients with SLE to endothelial cells stimulated with TNF alpha may be due to the ability of this cytokine to increase the expression of potential antigens on the surface of these cells. Hence, TNF alpha may play a role in the immune-mediated vascular damage associated with SLE.
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PMID:Sera from patients with systemic lupus erythematosus demonstrate enhanced IgG binding to endothelial cells pretreated with tumour necrosis factor alpha. 858 27

Systemic lupus erythematosus (SLE) manifested with multiple autoantibodies production and glomerulonephritis, is the best example of systemic autoimmune diseases. To further elucidate the role of cytokines and the potential involvement of natural killer cells (NK cells) in the pathogenesis of lupus, phenotypic analysis of peripheral blood mononuclear cells (PBMC), NK cells cytotoxicity and cytokines production pattern of SLE patients and normal controls were examined. In addition, the effect of a variety of cytokines on anti-dsDNA antibodies production was also investigated. Our results showed that: (a) there was an increased percentage of memory T cells and decreased percentage of NK cells in SLE patients when compared to normal controls (p < 0.05); (b) a decreased production of cytokines like gamma-IFN in mitogen-stimulated PBMCs was also noted in SLE patients; (c) cytolytic activity of NK cells was markedly reduced in SLE patients (p < 0.05); (d) spontaneous secretion of IgG anti-dsDNA antibodies by B cells isolated from SLE patients could be inhibited by gamma-IFN, but not by IL-2, IL-4 and IL-5. These data suggested that decreased functions of NK cells and related type 1 T helper cells be closely related to the immune dysregulation and autoantibodies production in SLE.
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PMID:Phenotypic and functional analysis of natural killer cells in systemic lupus erythematosus patients. 860 62


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