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)

When measured serially by Farr assay at a frequency of approximately once a month, changes in levels of anti-dsDNA appear to be a good predictor of clinical disease activity. Although the role of antibodies to the RNA component of snRNP awaits further studies, measurement of anti-UsnRNP antibody levels seems to be of limited value in monitoring lupus patients in clinical practice. The same holds for antibodies to SSA (Ro) and anti-histone antibodies. More recently described antibodies to C1q are probably useful in the follow-up of SLE patients suspected of proliferative renal involvement. The best alternative to measuring levels of the antibodies mentioned before is probably serial analysis of activation of the complement cascade. Levels of complement factors like C3, C4 and, functionally, CH50 remain a useful parameter for monitoring disease activity in SLE, although fluctuations in anti-dsDNA as measured by Farr assay seem superior with respect to sensitivity and specificity for an ensuing relapse. Despite the problems in sampling, measuring levels of activated split products of complement factors like C3a, C3d or C5a may prove to be a valuable tool in the follow-up of lupus patients. The involvement of the endothelial surface is illustrated by rising sVCAM-1 levels prior to relapses in SLE. Although one could expect that subsequent inflammation should be reflected by increased levels of inflammatory molecules like CRP and IL-6, the use of these molecules as predictors of lupus activity seems limited. Interferon-alpha as a direct reflector of the effector phase seems, however, rather promising in this respect and awaits longitudinal studies to analyse the possible relation with clinical disease activity and other serological parameters.
Lupus 1995 Apr
PMID:Serological markers of disease activity in systemic lupus erythematosus. 779 29

Cytokines are important in developmental and effector pathways of lymphocyte function. Our objective was to elucidate the profile of cytokines produced by circulating mononuclear cells from patients with systemic lupus erythematosus as estimated from studies of cytokine-gene activation. cDNA prepared by reverse transcription of lymphocyte mRNA was amplified using the polymerase chain reaction and normalized on the basis of beta-actin gene expression. Of 10 cytokines investigated in 16 individuals, differences between SLE and controls were found in only three. IL-2 transcripts were detected in four of six cases of subjects hospitalized for active SLE, but in only one of seven healthy controls, and none of three cases with pulmonary tuberculosis. By contrast, IL-4 transcripts were decreased compared with healthy controls and patients with tuberculosis. Also, TGF beta transcripts appeared to be decreased in SLE. All individuals studied regularly demonstrated high levels of transcripts for IL-1 beta, IL-6 and TNF alpha and transcripts for IFN gamma, TNF beta, IL-5 and IL-10 were variably expressed. In a second group of six SLE patients with less active disease, there was also a decrease in IL-4 expression compared with six healthy controls. Moreover, assays performed on sera from patients with active SLE revealed that IL-4 levels were not increased. Although in mice this cytokine has a well documented role in supporting antibody production, this study provides no evidence that IL-4 is involved in the B cell hyperactivity characteristic of human SLE.
Lupus 1994 Oct
PMID:Cytokine gene profile in circulating blood mononuclear cells from patients with systemic lupus erythematosus: increased interleukin-2 but not interleukin-4 mRNA. 784 98

The MRL-lpr/lpr and MRL-(++) mice were studied for the expression of cytokines in the spleen, lymph node, thymus, kidney and brain through the reverse transcription-polymerase chain reaction (RT-PCR). The frequencies of IL-4 and TNF-alpha expression in the thymus and spleen were significantly higher in MRL-lpr/lpr mice than in MRL-(++) mice from the age of 17 to 32 weeks. More importantly, IL-4 transcript was demonstrated in the early rather than in the terminal stage of the lupus disease. At the 20th week, MRL-lpr/lpr mice with active disease exhibited higher concentrations of IL-1 alpha, IL-6 and TNF-alpha in serum than MRL-(++) mice. Interestingly, in MRL-lpr/lpr but not MRL-(++) mice, the IL-6 concentration in cultured supernatants of the thymic cells was significantly higher than that of the splenic or lymph node cells. On the other hand, IL-6 and IL-1 beta were expressed in the brain and kidney of MRL-lpr/lpr mice but not of MRL-(++) mice. Cultured MRL-lpr/lpr mesangial cells could also express IL-6 but to a lesser extent. These results suggest that the abnormal splenic and thymic IL-4 and TNF-alpha expression may predispose the development of autoimmune reactions. The expression of IL-1 beta and IL-6 in the brain and kidney may be implicated in the damage of these two organs in MRL-lpr/lpr mice.
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PMID:Abnormal splenic and thymic IL-4 and TNF-alpha expression in MRL-lpr/lpr mice. 786 62

IL-6, soluble IL-6 receptor and IgG with anti-IL-6 activity were measured in the plasma of 14 lupus patients and 10 normal subjects. The capacity of peripheral blood mononuclear cells to spontaneously produce IL-6 in vitro was also measured. Our results indicate that IL-6 plasma levels in patient plasma as measured by ELISA were not different from normal but that supernatant levels were significantly lower than normal (P < 0.05). In vitro IgG production was comparable for all lupus patients' cells irrespective of the in vitro IL-6 levels. Plasma soluble IL-6 receptor levels directly correlated with IL-6 production capacity of SLE cells and the ratio of soluble receptor to anti-IL-6 directly correlated with IL-6 production in patients but not in normals. Inhibition assays demonstrated competition between anti-IL-6 and soluble receptors for IL-6 and the inhibition by plasma of IL-6 binding to monoclonal anti-IL-6. We believe the interaction of anti-IL-6 and IL-6 receptor with IL-6 may contribute to the homeostasis in IL-6 activity in vivo and skewing of the soluble receptor/anti-IL-6 ration may contribute to the lupus disease process.
Lupus 1994 Jun
PMID:Anti-interleukin-6 and soluble interleukin-6 receptor in systemic lupus erythematosus. 795 1

We report on a patient with splenic lymphoma of B-cell origin who developed autoimmune hemolytic anemia (AIHA). IgM lambda M-protein, IgM anticardiolipin antibody (ACA), and lupus anticoagulant (LA) were detected in the serum, and direct Coombs' test showed autoantibodies of the IgG1 and IgG2 subclasses on red blood cells (RBC). In in vitro culture, tumor cells isolated from the spleen produced only IgM ACA, which was enhanced by IL-6 but not by IL-4 or IL-5. The levels of ACA and LA decreased after splenectomy and chemotherapy; the strength of the direct Coombs' test, however, did not change. These findings indicated that in this patient the lymphoma cells produced IgM lambda ACA, but not autoantibodies of the IgG1 and IgG2 subclasses against RBC. It was also suggested that IL-6 might at least partially stimulate the production of ACA.
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PMID:Multiple autoantibody production in a patient with splenic lymphoma. 801 67

To investigate the role of IL-6 in systemic lupus erythematosus (SLE), we selectively inhibited IL-6 in lupus-prone NZB/NZW F1(B/W) mice by chronic administration of a rat mAb to mouse IL-6. Anti-IL-6 alone elicited an anti-rat response that blocked its biologic effects. To circumvent this problem, we rendered B/W mice tolerant to the rat mAb by administration of anti-CD4 concurrent with the first dose of anti-IL-6. Thereafter, the mice received weekly injections of anti-IL-6 alone. There were two control groups: one group received the tolerizing regimen of anti-CD4 along with a control rat IgG1 mAb (GL113) instead of anti-IL-6; the other control group received PBS. Mice that received anti-CD4 were tolerant to the rat mAb for 6 mo. Throughout this period, treatment with anti-IL-6 prevented production of anti-dsDNA, significantly reduced proteinuria, and prolonged life. Mice that received anti-IL-6 without anti-CD4 developed an immune response to the rat mAb and then developed anti-dsDNA antibodies, proteinuria, and mortality comparable with control mice. These findings establish that IL-6 promotes autoimmunity in B/W mice. They further indicate that, although mAb to IL-6 can suppress murine lupus, the development of host immunity to the mAb abrogates its beneficial effects. Finally, this is the first study to demonstrate that a brief course of anti-CD4 can induce tolerance to another therapeutic mAb, in this case an anti-cytokine mAb.
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PMID:Interleukin 6 promotes murine lupus in NZB/NZW F1 mice. 804 Mar 14

Enrichment of diet with omega-3 lipid rich-menhaden fish oil (FO) when fed ad libitum to autoimmune lupus-prone NZB/NZW F1 (B/W) female mice delayed the onset and slowed progression of renal disease while significantly extending life-span compared to omega-6 lipid rich-corn oil (CO)-fed mice. Northern blot analysis of kidneys from FO-fed mice revealed no detectable levels of IL-1 beta, IL-6 and TNF alpha mRNA contrasted to levels that were easily detected in CO-fed mice. In contrast to the cytokines, FO-fed mice showed higher renal levels of the antioxidant enzymes-catalase, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD)-mRNAs compared to CO-fed mice. The results suggest that dietary supplementation with FO, as compared to CO, inhibits the production of pro-inflammatory cytokines and ameliorates immune-complex-mediated kidney injury possibly by enhancing the ability of cells to dispose of harmful reactive oxygen intermediates.
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PMID:Decreased pro-inflammatory cytokines and increased antioxidant enzyme gene expression by omega-3 lipids in murine lupus nephritis. 817 24

Previous studies in our laboratory demonstrated an altered immuno-endocrine feedback communication via the hypothalamo-pituitary-adrenal (HPA) axis, which may be an important modulatory factor in the development of spontaneous autoimmune thyroiditis in Obese strain (OS) chickens. These birds show a significantly lower, or even absent, increase in serum glucocorticoid levels in response to an intravenous injection of antigen or conditioned medium (CM) from mitogen-stimulated spleen cells known to contain glucocorticoid-increasing factors (GIFs), notably interleukin-1 (IL-1). The present study was aimed at investigating this feedback regulation in animal models with spontaneous systemic autoimmune diseases, such as the UCD-200 chicken, which serves as a model for human scleroderma, and various murine lupus models. In contrast to OS chickens, UCD-200 chickens displayed a nearly normal plasma corticosterone surge in response to CM, and IL-1 was again identified as the primary GIF in CM. Recombinant IL-1 also induced a drastic increase in plasma corticosterone levels in various strains of normal mice. A similar increase was observed in the bacterial lipopolysaccharide-resistant C3H/HeJ strain, thus excluding the possibility of bacterial endotoxin contamination. However, in young lupus-prone (NZB/W)F1 and MRL/MP-lpr mice, a significantly lower increase in plasma corticosterone levels was observed after injection of recombinant IL-1, suggesting a deficient immuno-endocrine communication via the HPA loop in this instance as well. Detailed studies to identify further cytokines with GIF activity in the avian and murine systems showed that both IL-6 and tumor necrosis factor-alpha could induce increased plasma corticosterone levels in mice, but not in chickens. IL-3, IL-8, transforming growth factor-beta, interferon-gamma and granulocyte-macrophage colony-stimulating factor were devoid of GIF activity in both chickens and mice.
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PMID:Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease. 821 76

Murine lupus and the analogous human disease systemic lupus erythematosus (SLE) in humans are characterized by multisystem disease accompanied by the production of numerous serum autoantibodies. The classic model of murine lupus is the New Zealand black mouse (NZB). In this strain anti-DNA antibodies are the most specific marker for the presence of murine lupus, in that this autoantibody parallels both the development and activity of the disease. Exposure to ultraviolet (UV) radiation is known to exacerbate the disease in both the murine and the human disease. UV irradiation of the skin increases serum levels of certain cytokines including interleukin-1 (IL-1), IL-6, and granulocyte/macrophage-colony stimulating factor (GM-CSF), which can influence B- and T-cell function. Recent studies have focused on the role of cytokines in SLE. We hypothesize that the ultraviolet (UV)-induced exacerbation in NZB mice in part is mediated by UV-induced cytokines such as IL-1. Eight-week-old female NZB and DBA/2 mice were exposed to UV irradiation. Sera and supernatants from spleen cell cultures were assayed for anti-DNA antibodies. After UV exposure, NZB mice showed a marked increase in such antibodies. Skin from both strains of mice was probed for IL-1 alpha mRNA before and after UV irradiation. At 24 h, DBA/2 mice had a slight increase in mRNA coding for IL-1 alpha, whereas a much greater increase in skin IL-1 alpha was seen in the NZB skin. This increase in IL-1 mRNA was associated with similar increases in IL-1 bioactivity. These data suggest that the mechanism underlying the UV-induced exacerbation of lupus is mediated in part by the cutaneous production of IL-1.
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PMID:Epidermal cytokines in murine lupus. 842 94

The murine MRL/lpr model of lupus nephritis is characterized by a systemic autoimmune syndrome closely resembling the human disease. The lpr mutation represents a defect in the expression of the apoptosis-signaling Fas antigen gene which causes accelerated autoimmune disease in MRL/ lpr mice and a milder, non-lethal autoimmune syndrome in C57BL6-lpr/lpr mice. The role of cytokines in autoimmune pathogenesis and its relationship with the lpr mutation remains poorly understood. In this study we utilized a RNase protection assay to quantitatively and simultaneously examine the expression of 10 different cytokine genes, namely IL-1 alpha, II-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IFN-gamma, TNF-alpha, and TNF-beta in kidney, spleen, liver, and lymph nodes obtained from pre-diseased and diseased lupus-prone MRL/lpr, pre-diseased MRL/+2 and C57BL/6-lpr mice, as well as healthy non-autoimmune C57BL/6 and Balb/c mice. Diseased MRL/lpr mice demonstrated marked and predominant IL-1 beta gene upregulation in kidneys, liver, lymph nodes and spleen. Increased message for both TNF-alpha and IFN-gamma genes was also observed in lymph nodes, and less consistently, in the spleen, and kidneys derived from diseased MRL/lpr mice as compared to pre-diseased MRL/+2 or normal nonautoimmune control mice. Furthermore, a modest increase in the expression of both IL-1 beta and IFN-gamma message was observed in lymphoid organs of pre-diseased MRL/lpr and C57BL/6-lpr mice compared with MRL/+2 and C57BL/6 controls, respectively. Increased IL-1 beta gene expression was associated with the presence of the lpr mutation, was observed during the prediseased stage, and increased during active disease in both male and female mice. In summary, these results demonstrate that generalized up-regulation of IL-1 beta gene expression, in concert with a more limited up-regulation of both TNF-alpha and IFN-gamma expression, are prominent features of the autoimmune syndrome in the MRL/lpr model of SLE and may contribute to the disease-accelerating effect of the lpr mutation.
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PMID:Cytokine gene expression in the MRL/lpr model of lupus nephritis. 880 76


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