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

We investigated the role of natural killer (NK) cells in the development of autoantibody production in which (C57BL/6 x DBA/2) F1 (BDF1) hybrid mice were injected intravenously with spleen cells (SC) from parental DBA/2 mice (treated BDF1 mice). Treated BDF1 mice began to show an increase in serum anti-dsDNA antibody 2 weeks after injection, while the NK activity of their SC transiently increased initially in the first 1 to 2 weeks after injection, but subsequently decreased dramatically. Flow cytometric analysis suggested that this sequential change in NK activity correlated with the absolute number of host-derived NK1.1+ cells in SC from treated BDF1 mice. We demonstrated that the level of anti-dsDNA in serum is directly influenced by the level of NK activity in treated BDF1 mice. Depletion of NK cells by administration of anti-NK1.1 mAb accelerated the development of autoantibody production, whereas augmentation of NK activity by administration of poly-(I:C) inhibited the development of autoantibody production. This inhibitory effect of poly(I:C) was abolished by prior depletion of NK cells. Interestingly, suppression of autoantibody production was seen only when poly(I:C) was administrated within 1 week after injection of parental SC. Last, we demonstrate that adoptive transfer of interleukin-2 (IL-2)-activated NK cells had a protective effect against the development of autoantibody production. These findings imply that NK cells may have a protective role in lupus-like disease especially in its early stage. In addition, it opens up the possibility that adoptive immunotherapy with IL-2-activated NK cells can delay or even prevent the development of autoimmune disease.
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PMID:Natural killer cells inhibit the development of autoantibody production in (C57BL/6 x DBA/2) F1 hybrid mice injected with DBA/2 spleen cells. 786 84

This study was designed to explore the prevalence and clinical significance of elevated antiphospholipid antibodies (APA) titres in patients affected by acute myeloid leukemia (AML) and high-grade non-Hodgkin's lymphoma (NHL). We also analyzed possible correlations with circulating levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and the soluble form of the receptor for interleukin-2 (sIL-2r). Nineteen patients with de novo AML and 14 patients with newly-diagnosed NHL were investigated. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Five patients with AML (26.3%) and 5 patients with NHL (35.7%) presented elevated APA at diagnosis, as compared to 3 of 174 persons of the control group (p < 0.0001). APA titres became normal in all patients responding to treatment, whereas non-responders retained elevated levels. In addition, 6 patients (4 with AML and 2 with NHL), who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or ACA positivity. At presentation, the mean levels of IgG- and IgM-ACA in patients were not significantly different from controls, and concordance between ACA and LA results reached just 30%. 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 sIL-2r in NHL were found significantly elevated compared to controls (p = 0.003, p = 0.009 and p = 0.024 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antiphospholipid antibodies: prevalence, clinical significance and correlation to cytokine levels in acute myeloid leukemia and non-Hodgkin's lymphoma. 811 79

Systemic lupus erythematosus (SLE) is an important autoimmune disease with multiple organ system involvement. From preliminary studies, we have found that six Chinese herbs: Atractylodes ovata, Anqelica sinensis, Cordyceps sinensis, Liqustrum lucidum, Codonopsis pilosula and Homo sapiens can improve defective in vitro interleukin-2 (IL-2) production in patients with SLE. In order to investigate the in vivo effects of these herbs, we used NZB/NZW F1 mice, a typical lupus animal model used to test these herbs. It was found that C. pilosula, H. sapiens and C. sinensis could prolong the life span of female NZB/NZW F1 mice and inhibited anti-ds DNA production. Although A. sinensis could prolong the life span of experimental mice, it did not inhibit the production of anti-ds DNA antibody. These herbs may have great potential for the management of human SLE in the future.
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PMID:The effects of Chinese herbs on improving survival and inhibiting anti-ds DNA antibody production in lupus mice. 813 70

The plasma levels of interleukin-4 (IL-4), interleukin-2 (IL-2), soluble receptor of IL-2 (IL-2R) and T cell expression of IL-2 receptor chain (CD25+) were determined in an attempt to relate these parameters with disease activity in systemic lupus erythematosus (SLE). IL-4, IL-2 and sIL-2R plasma levels of SLE patients were significantly higher than those of the control group (P < 0.05) while CD25+ expression was similar in both groups. Only sIL-2R levels were significantly higher (P < 0.05) in active than in inactive patients.
Lupus 1993 Aug
PMID:Relationship of IL-2, IL-2R (CD25+), soluble IL-2R and IL-4 with disease activity in SLE patients. 826 74

Several experimental conditions were used in this study to evaluate the in vitro effects of 15-deoxyspergualin on the function of T lymphocytes, B lymphocytes and monocytes from healthy subjects and patients suffering from systemic lupus erythematosus. Whilst the secretion of polyclonal immunoglobulin (Ig) M and IgG from the B lymphocytes of the healthy subjects was diminished by 15-deoxyspergualin, neither the proliferative response of normal T and B cells to mitogenic stimulation nor the cytokine secretory capacity of these cells (e.g. interleukin-2, -4, -6 and gamma-interferon) and monocytes (e.g. interleukin-1 beta and -6) were affected by the drug. In contrast, on the mononuclear cells obtained from the lupus patients not only did 15-deoxyspergualin inhibit the spontaneous production of polyclonal and anti-DNA IgG antibodies but also suppressed interleukin-1 beta secretion from the monocytes. Other functional responses of T and B cells and monocytes from lupus patients, including mitogenic activation and cytokine secretion, were not altered by the drug. These data suggest that 15-deoxyspergualin possesses a novel mechanism of pharmacological immunosuppression apparently different from that of other immunosuppressants, such as cyclosporin A, FK506 and corticosteroids, that seems to be primarily displayed at the level of autoreactive B cells and monocytes.
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PMID:Immunosuppressive activity of 15-deoxyspergualin on normal and autoimmune peripheral blood mononuclear cells. 889 2

Lymphocyte B hyperactivity and cell-mediated immune deficiency are characteristic features of systemic lupus erythematosus. This imbalance is seen in cytokine production. T lymphocyte production of interleukin-2 is defective while proinflammatory cytokines such as IL1 beta, IL6 and TNF alpha increase spontaneously during flare-ups. However, the capacity of the monocytes in these patients to produce cytokines is reduced after stimulation by exterior agents such as LPS. Moreover, production of interleukin 10 is increased in lupus patients. Most likely, it is this increase in interleukin 10 production which causes the disrupted immunity in this disease.
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PMID:[Cytokines and lupus]. 909 58

We investigated whether the immunosuppressive effect of bromocriptine in mice is due to its direct effect on lymphocyte functions or through inhibition of prolactin secretion. Incubation of mouse Babl/c splenic lymphocytes with bromocriptine in vitro at a concentration of around 0.5 to 1 microgram/mL causes an inhibition of antigen- or mitogen-induced proliferation. However, bromocriptine in vitro has no effect on lymphokine production (gamma-interferon and interleukin-2), expression of interleukin-2 receptor or lymphocyte cytotoxic function. Furthermore, treatment of Babl/c mice with bromocriptine inhibits the mixed lymphocyte reaction and mitogen stimulation, as well as primary and secondary antibody production. However, we postulated that the inhibition of ex vivo functional activity could not account for a direct cytostatic or cytotoxic effect of bromocriptine. This is supported by the in vitro data, which shows that bromocriptine has no effect on proliferating P-815 mastocytoma tumor cells. Finally, (NZB/NZW) F1 mice spontaneously develop a disease similar to systemic lupus erythematosus. In both non-autoimmune Babl/c mice and (NZB/NZW) F1 lupus-mice, the serum level of bromocriptine achieved by a treatment with 5 mg/kg on average is 2-6 ng/mL. On the one hand, this dose is sufficient to significantly alter the ex vivo functional tests in Babl/c mice and to show a beneficial effect in the in vivo model of female lupus-mice. On the other hand, the lowest concentration which could have an inhibitory effect on antigen- and mitogen-induced proliferation in vitro is 200 ng/mL, ie 50 times more than that required in vivo to obtain significant reductions of proteinurea, glomerular membrane proliferation and immune deposits in lupus-mice. The serum levels of gamma-interferon and interleukin-2 are reduced in lupus-mice when compared with Babl/c mice. The treatment with bromocriptine does not influence these parameters. In conclusion, our data demonstrate that the major immunosuppressive activity of bromocriptine is probably dependent on its hypoprolactinemic effect.
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PMID:Bromocriptine has little direct effect on murine lymphocytes, the immunomodulatory effect being mediated by the suppression of prolactin secretion. 918 Oct 47

Systemic lupus erythematosus (SLE) is a highly heterogeneous disorder in which multiple immunologic abnormalities have been described. In this review, we thoroughly analyse the impaired T cell production of, and response to, interleukin-2 (IL-2) characteristic of patients with SLE. Since it was first reported, several articles have provided us with enlightening, but somewhat confusing, data that reveal the complexity of the subject. The IL-2 production by T cells is part of a complex network in which a discrete alteration is capable of disrupting the whole system. On the other hand, regulatory mechanisms exist that, in an attempt to compensate the primary alteration, provoke secondary defects. Evidence indicates that this defect is not intrinsic, but rather, results from multiple microenvironmental influences that act on the T cell and modify its activation state and its cytokine production. Abnormalities in co-stimulatory mechanisms and in cytokines that may be related to the IL-2 production deficiency, have been described in patients with SLE. We also consider the information derived from murine SLE models, IL-2 knockout models and reports concerning the immune dysregulation present in patients with SLE.
Lupus 1998
PMID:Interleukin-2 and systemic lupus erythematosus--fifteen years later. 964 9

We have investigated the effects of interleukin-2 (IL-2) and transforming growth factor-beta (TGF-beta) gene therapy on the progress of autoimmune disease in MRL-lpr/lpr mice, a murine model of systemic lupus erythematosus (SLE). These mice have uncontrolled proliferation of T cells, an impaired response to T cell mitogen and produce autoantibodies against nuclear antigens, including DNA. Immune complexes formed by these autoantibodies are believed to cause glomerulonephritis and vasculitis in lupus mice and human SLE. Since there is an imbalance of cytokine production in both SLE patients and lupus mice, we examined the effects of cytokine gene therapy on the progression of autoimmune disease in MRL-lpr/lpr mice. The mice were treated orally with a non-pathogenic strain of Salmonella typhimurium bearing the aroA-aroD- mutations and carrying the murine genes encoding IL-2 and TGF-beta. The bacteria synthesise and slowly release the cytokines in vivo. Our results show that, contrary to expectation, TGF-beta gene therapy produced no improvement in pathology and generally had opposite effects to those of IL-2. IL-2 gene therapy restored the defective T cell proliferative response to mitogen and suppressed the autoantibody response, glomerulonephritis and growth of lymphoid tumours.
Lupus 1999
PMID:Modulation of autoimmune disease in the MRL-lpr/lpr mouse by IL-2 and TGF-beta1 gene therapy using attenuated Salmonella typhimurium as gene carrier. 1002 97

We have recently reported that transforming growth factor-beta (TGF-beta) co-stimulates interleukin-2 (IL-2) activated CD8+ T cells to down-regulate antibody production. In SLE, lymphocyte production of both IL-2 and TGF-beta is decreased. Here we report that a brief treatment of PBMC from SLE patients with IL-2 and TGF-beta can result in marked inhibition of spontaneous polyclonal IgG and autoantibody production. Peripheral blood mononuclear cells (PBMC) from 12 patients with active SLE were exposed to IL-2 with or without TGF-beta for three days, washed and cultured for seven more days. The mean decrease in IgG secretion was 79%. The strongest inhibitory effect was observed in cases with the most marked B cell hyperactivity. Spontaneous production of anti-nucleoprotein (NP) antibodies was observed in four cases and cytokine treatment of PBMC decreased autoantibody production by 50-96%. IL-2 inhibited Ig production by either TGF-beta-dependent or independent mechanisms in individual patients. In a study of anti-CD2 stimulated IgG production in a patient with active SLE, we documented that IL-2 and TGF-beta reversed the enhancing effects of CD8+ T cells on IgG production and induced suppressive activity instead. These results raise the possibility that cytokine-mediated down-regulation of B cell hyperactivity in SLE may have therapeutic potential.
Lupus 1999
PMID:Cytokine-mediated down-regulation of B cell activity in SLE: effects of interleukin-2 and transforming growth factor-beta. 1019 2


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