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

The homeostasis of peripheral immune system function is maintained by the activity of regulatory lymphocytes. Among these cells, a subset of CD8+CD28- T suppressor lymphocytes has recently been characterized for the capacity to mediate their effects without antigen restriction. These non-antigen-specific CD8+ T suppressor lymphocytes originate from circulating CD8+CD28- T lymphocytes after stimulation with interleukin-2 and interleukin-10. CD8+ suppressor cells inhibit both antigen-specific CD4+ T cell proliferation and cellular cytoxicity through secretion of cytokines such as interferon-gamma, interleukin-6, and interleukin-10. The function of CD8+ suppressor cells is impaired in patients with systemic lupus erythematosus in relapse as well as in patients with systemic sclerosis with disease progression, suggesting the involvement of CD8+ suppressor cells in the pathogenesis of autoimmune diseases. Interestingly, CD8+ suppressor cells have been found among tumor-infiltrating lymphocytes, which could be related to tumor-induced-immunosuppression. Failure to generate CD8+ suppressor cells from the peripheral blood is frequently observed in HIV-infected patients. It remains to be clarified whether this phenomenon is due to depletion and/or functional impairment of this cell subset or to their compartmentalization in peripheral tissues and immunocompetent organs where they could contribute to the induction of immunodeficiency.
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PMID:Non-antigen specific CD8+ T suppressor lymphocytes. 1567 45

The polymorphism of the interleukin-10 (IL-10) promoter and tumor necrosis factor receptor II (TNFRII) in Vietnamese patients with systemic lupus erythematosus (SLE) was examined by using the polymerase chain reaction (PCR) method with genomic DNA and allele-specific primers. In the frequency of IL-10 promoter 1082 genotypes consisting of AA, A/G and GG, the allele frequency of G in the SLE patients was significantly higher than that in the healthy controls. On the other hand, there was no statistical difference in the frequency of TNF receptor (TNFR) II 196 genotypes between the SLE patients and healthy controls. It was therefore suggested that the polymorphism of the IL-10 promoter, but not TNFRII, might participate in the pathogenesis of SLE in Vietnamese.
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PMID:Polymorphism of interleukin-10 promoter and tumor necrosis factor receptor II in Vietnamese patients with systemic lupus erythematosus. 1567 53

The aim of this study was to determine whether tripterine, isolated from Tripterygium wilfordii Hoog f. in China, had beneficial effects on experimental systemic lupus erythematosus induced by active chromatin in BALB/c mice. BALB/c mice were immunized with active chromatin isolated from concanavalin A-activated syngenetic spleno-lymphocytes on day 0. Tripterine 6 or 12 mg kg(-1) day(-1), or prednisone 5 mg kg(-1) day(-1) was given to BALB/c mice intragastrically from day 35 to day 50. Treatment with tripterine 12 mg kg(-1) day(-1) for 15 days protected renal from glomerular injury with a concomitant reduction of serum autoantibodies and total immunoglobulin G (IgG) also with a improvement of splenocyte proliferation stimulated with concanavalin A and lipopolysaccharide. The effects were associated with reduced interleukin-10 production and serum nitric oxide (NO) level but not interferon-gamma compared with vehicle-treated control group. Tripterine 6 mg kg(-1) day(-1) had no significant protective effect against glomerular injury. It inhibited autoantibodies and interleukin-10 production but had no effect on splenocyte proliferation, serum NO level, and interferon-gamma production. These findings suggested that tripterine had a beneficial effect on systemic lupus erythematosus induced by active chromatin in BALB/c mice.
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PMID:Beneficial effect of tripterine on systemic lupus erythematosus induced by active chromatin in BALB/c mice. 1584 Apr 9

Although systemic lupus erythematosus (SLE) is indeed a complex autoimmune disease, recent advances in our understanding of lupus pathogenesis have suggested new, targeted approaches to therapy. The purpose of this review is to discuss the underlying scientific rationale and results of first clinical studies of new treatment approaches to SLE, with a focus on cell-depleting therapies and cytokine blockade. It has become clear that the B lymphocyte plays a key role in disease pathogenesis by both autoantibody-dependent and autoantibody-independent mechanisms. Additionally, aberrant interactions between B and T cells are critical to disease emergence and progression. New agents that directly target immune cells abnormal in SLE include the B-cell depleting or modulating antibodies, rituximab (anti-CD20) and epratuzumab (anti-CD22) and the anti-dsDNA tolerogen LJP394. Another promising approach has been to block co-stimulatory interactions between T and B cells, for example by inhibiting the CD40-CD40 ligand pathway with anti-CD40 ligand monoclonal antibody or the B7 pathway with CTLA-4Ig. Immune cells can also be manipulated indirectly through cytokine effects. For B cells, anti-BAFF (B-cell activation factor of the tumor necrosis family) provides an example of this approach. Other, more pleiotropic cytokines can likewise be blocked in SLE. In addition to the blockade of interleukin-10 (IL-10), the first anti-cytokine approach examined, it is mainly anti-tumor necrosis factor therapy that has come into focus, holding promise for some patients with lupus nephritis. The majority of the available data on these new treatment approaches stems from open-label trials, but controlled trials are under way. Moreover, many additional cytokines, such as interleukin (IL)-6, IL-18, and the type I interferons, represent interesting future targets.
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PMID:New treatments for SLE: cell-depleting and anti-cytokine therapies. 1615 Apr 7

To study the apoptosis of lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients and the possible role of IL-10 in this apoptosis involved in the pathogenesis of SLE, three color fluorescence and flow cytometry were used to investigate the early apoptosis of lymphocyte subsets from freshly separated or cultured peripheral blood mononuclear cells (PBMCs). ELISA was employed to detect the levels of IL-10 in serum and the levels of sFas and sFasL in cultured PBMC supernatants, and the results of sFas and sFasL were confirmed by real-time PCR of Fas and FasL mRNA. The results showed that in cells from SLE patients, the apoptosis of CD3+, CD4+, and CD8+ T cells was distinctly increased, and the percentage of CD4+ cells and the CD4/CD8 ratio was significantly decreased, as compared with normal controls. The apoptosis of T lymphocytes cultured with SLE serum was markedly higher than that of cells cultured with control's serum. Blockade of interleukin-10 (IL-10) activation by an anti-IL-10 antibody reduced the SLE serum induced apoptosis of CD4+ and CD8+ T cells. The levels of sFas and sFasL in the culture supernatant and Fas and FasL mRNA expressions in cultured cells were significantly higher in the SLE serum-cultured groups, but decreased evidently in the presence of the anti-IL-10 antibody. Above findings suggested that SLE cells showed abnormally high apoptosis of T lymphocytes, especially of the CD4+ subpopulation, resulting in a decreased CD4/CD8 ratio. The high percentage of apoptotic T cells in SLE patients may be related to the high levels of IL-10 in SLE serum, as IL-10 may induce the abnormally activated T cells to trigger apoptosis via the Fas-FasL pathway.
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PMID:The abnormal apoptosis of T cell subsets and possible involvement of IL-10 in systemic lupus erythematosus. 1622 34

T cell immune responses play important roles in the pathogenesis of systemic lupus erythematosus (SLE). (S)-Armepavine (C19H23O3N; MW313) from Nelumbo nucifera suppresses T cells proliferation. To study its potential benefit on SLE, we examined effects of (S)-armepavine on MRL/MpJ-lpr/lpr mice, which have similar disease features to human SLE. MRL/MpJ-lpr/lpr mice were treated orally with (S)-armepavine for 6 weeks and their SLE characteristics were evaluated. The results revealed that (S)-armepavine prevented lymphadenopathy and elongated life span of MRL/MpJ-lpr/lpr mice. It seemed to be mediated by inhibition of splenocytes proliferation, suppression of interleukin-2 (IL-2), interleukin-4, interleukin-10, and interferon-gamma (IFN-gamma) gene expressions, reduction of glomerular hypercellularity and immune complexes deposition, and decrease of urinary protein and anti-double stranded DNA autoantibody production. Furthermore, the data demonstrated (S)-armepavine impaired IL-2 and IFN-gamma transcripts in human peripheral blood mononuclear cells. We suggest that (S)-armepavine may be an immunomodulator for the management of autoimmune diseases like SLE.
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PMID:Inhibition of (S)-armepavine from Nelumbo nucifera on autoimmune disease of MRL/MpJ-lpr/lpr mice. 1641 31

The objective of the study is to examine whether interleukin-10 (IL-10) promoter polymorphism is a marker of susceptibility of systemic lupus erythematosus (SLE) in Chinese patients in Taiwan. The study included 119 Chinese patients with SLE. One hundred unrelated healthy individuals living in central Taiwan served as control subjects. Each polymorphism was detected as a result of a polymerase chain reaction (PCR)-based restriction analysis. The PCR product length was determined to be 412 bp (CC) whereas two fragments of 236 and 176 bp were determined to be excisable lengths (AA). The relationship between the IL-10 gene polymorphism and clinical manifestations of SLE was evaluated. For the genotype and allelic frequency, there were statistically significant differences between the SLE patients and the normal control subjects (p=0.007 and 0.003, respectively). But we did not detect any association of carriage rate of the IL-10 polymorphism and the normal control subjects (p=0.077). Furthermore, we did not detect any association of IL-10 genotype with antinuclear antibody, malar rash, photosensitivity, discoid lupus, mucosal ulcer, arthritis, serositis, hematology, immunology, involvement of central nervous system, and renal disease involvement in the SLE patients. The significant relation of -627 IL-10 genotype and allelic frequency with SLE implies that the IL-10 gene polymorphism can serve as a candidate gene marker for further study in patients with SLE in Taiwan.
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PMID:The association of -627 interleukin-10 promoter polymorphism in Chinese patients with systemic lupus erythematosus. 1682 68

We are about to enter a new era in the treatment of patients with systemic lupus erythematosus (SLE). For the past 40 years hydroxychloroquine sulfate and corticosteroids, together with varying combinations of immunosuppressive drugs, have been the main treatments for SLE. Although effective for many patients, some patients fail to respond to these drugs and even more suffer from major side effects due to the generalized nature of the immunosuppression. In this article we review the remarkable confluence of new therapies ranging from newer immunosuppressive drugs with fewer side effects, such as mycophenolate mofetil, to the more targeted approaches offered by biological agents. These agents have been designed to block molecules such as CD20, CD22 and interleukin-10 that are thought to have an integral part in the development of SLE. This wolf might not yet be about to become extinct but its survival is increasingly under threat!
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PMID:Systemic lupus erythematosus--2005 annus mirabilis? 1693 74

Cancer immunosuppression evolves by constitution of an immunosuppressive network extending from a primary tumour site to secondary lymphoid organs and peripheral vessels and is mediated by several tumour-derived soluble factors (TDSFs) such as interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF). TDSFs induce immature myeloid cells and regulatory T cells in accordance with tumour progression, resulting in the inhibition of dendritic cell maturation and T-cell activation in a tumour-specific immune response. Tumour cells grow by exploiting a pro-inflammatory situation in the tumour microenvironment, whereas immune cells are regulated by TDSFs during anti-inflammatory situations--mediated by impaired clearance of apoptotic cells--that cause the release of IL-10, TGF-beta, and prostaglandin E2 (PGE2) by macrophages. Accumulation of impaired apoptotic cells induces anti-DNA antibodies directed against self antigens, which resembles a pseudo-autoimmune status. Systemic lupus erythematosus is a prototype of autoimmune disease that is characterized by defective tolerance of self antigens, the presence of anti-DNA antibodies and a pro-inflammatory response. The anti-DNA antibodies can be produced by impaired clearance of apoptotic cells, which is the result of a hereditary deficiency of complements C1q, C3 and C4, which are involved in the recognition of phagocytosis by macrophages. Thus, it is likely that impaired clearance of apoptotic cells is able to provoke different types of immune dysfunction in cancer and autoimmune disease in which some are similar and others are critically different. This review discusses a comparison of immunological dysfunctions in cancer and autoimmune disease with the aim of exploring new insights beyond cancer immunosuppression in tumour immunity.
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PMID:Cancer immunosuppression and autoimmune disease: beyond immunosuppressive networks for tumour immunity. 1700 5

Several linkage analyses have consistently shown that systemic lupus erythematosus (SLE) susceptible genes are located on chromosome 1q21-44. In this study, two major candidate genes, interleukin-10 (IL-10) and Fc gamma receptor IIa (FcgammaRIIa), within these regions were investigated in Thai SLE patients. The genotyping of three single-nucleotide polymorphisms (promoter area: -1082, -819 and -592) within IL-10 gene and one polymorphism (change amino acid at position 131) within FcgammaRIIa gene was determined in 195 SLE patients and 159 ethnically matched controls. The RR/RH genotypes of FcgammaRIIa were found to be significantly increased in SLE patients compared with healthy controls [OR = 2.01, 95% confidence interval (CI) = 1.28-3.14, P= 0.001]. Interestingly, the synergistic effect between RR/RH genotypes of FcgammaRIIa and ACC/ACC haplotype of IL-10 in susceptibility to SLE was observed (OR = 7.84, 95% CI = 1.60-52.04, P= 0.002). In addition, the FcgammaRIIa, RR homozygotes was also strongly associated with anticardiolipin antibody production (OR = 6.09, 95% CI = 1.38-30.54, P= 0.006). The result demonstrated that ACC haplotype of IL-10 gene and FcgammaRIIa R131 polymorphism can be used as marker for genetic susceptibility and severity to SLE in Thai population, particularly individuals carrying both specific genotypes.
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PMID:The synergistic effect of FC gamma receptor IIa and interleukin-10 genes on the risk to develop systemic lupus erythematosus in Thai population. 1709 53


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