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)

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

Two TNF binding proteins have been characterized as soluble fragments of TNF receptors. We measured the plasma concentrations of soluble type A (p75) and type B (p55) TNF receptors in patients with systemic lupus erythematodes (SLE), progressive systemic sclerosis (PSS), and mixed connective tissue disease (MCTD). In SLE and PSS patients plasma concentrations of both types of TNF receptors and in MCTD patients type A TNF receptors were significantly elevated compared to controls. Plasma concentrations of both soluble TNF receptors were highly correlated in SLE, PSS, and MCTD patients, indicating a possible coregulation of both TNF receptors. In contrast, soluble interleukin 2 receptor (sCD 25) plasma concentrations were not correlated and seem to be an independent parameter. The soluble forms of the TNF receptors neutralize TNF in cytotoxicity assays and are functionally active as TNF antagonists. In one patient with SLE, autoantibodies against type A TNF receptors were detected, TNF alpha, and TNF beta did not interfere with the autoantibody binding to the receptor.
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PMID:Evaluation of soluble tumor necrosis factor (TNF) receptors and TNF receptor antibodies in patients with systemic lupus erythematodes, progressive systemic sclerosis, and mixed connective tissue disease. 824 78

Cytokines are believed to play an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, for tumour necrosis factor alpha (TNF-alpha) both beneficial and deleterious effects have been reported. To obtain information about the involvement of this cytokine in the pathophysiology of SLE, serum levels of TNF-alpha, the soluble forms of the 55 and 75 kDa tumour necrosis factor receptors (TNF-R55 and TNF-R75), and interleukin-6 (IL-6) were measured by ELISA in nine female patients over a period of 2 yr. Compared to healthy controls, levels of TNF-alpha (median 47 pg/ml, range < 15-222 pg/ml), TNF-R55 (median 1.9 ng/ml, range 0.8-10.8 ng/ml), TNF-R75 (median 4.7 ng/ml, range 1.5-15 ng/ml) and IL-6 (median 3.5 pg/ml, range < 3.5-52 pg/ml) were significantly elevated in SLE patients (P < 0.0001 vs controls in all cases). There were strong correlations between TNF-alpha and its soluble receptors (P < 0.0001). Moreover, TNF-alpha and both TNF-Rs strongly correlated with clinical and serological parameters of disease activity, such as the European Consensus Lupus Activity Measurement (ECLAM) score, anti-dsDNA antibodies, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and anaemia (P < 0.0001 for all comparisons). TNF-alpha and TNF-R75 also correlated with IL-6 (P < 0.0001). However, no correlation between IL-6 and ECLAM was found, and the correlation of IL-6 with anti-dsDNA was relatively weak; in contrast, IL-6 correlated strongly with CRP and ESR (P < 0.0001). Although these data do not allow us ultimately to discriminate between beneficial and deleterious effects of TNF-alpha, they nevertheless suggest a central role for the TNF system in the pathophysiology of SLE.
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PMID:Tumour necrosis factor alpha and its soluble receptors parallel clinical disease and autoimmune activity in systemic lupus erythematosus. 894 91

Development of either Th1 or Th2 cell subsets has profound immunologic consequences, either pathogenic or protective, in several autoimmune diseases. However, it remains unclear which subset of Th cells plays a more critical role in lupus. In this study, we examined IL-4 and IL-12, which play decisive roles in the development of Th2 and Th1, respectively, in the IgG autoantibody production and development of lupus nephritis in NZB/W (B/W) F1 mice. Transfer of either IL-4- or IL-12-stimulated splenocytes from 5-mo-old B/W F1 mice into B/W F1 mice of the same age enhanced the production of IgG anti-dsDNA Ab. Consistently, administration of mAb against either IL-4 or IL-12 before the onset of lupus could inhibit the production of IgG anti-dsDNA Ab. However, only anti-IL-4 mAb was effective in preventing the onset of lupus nephritis. This discrepancy appeared to be explained by the differential effect on the production of IgG3-type autoantibody and TNF production. Interestingly, when combined, anti-IL-12 mAb abrogated the beneficial effect of anti-IL-4 mAb. These results indicate that both Th2 and Th1 contribute to the IgG autoantibody production, and IL-4 and IL-12 play key roles in the complexity of cytokine regulation in the pathogenesis of autoimmunity in lupus, but the former is more critical.
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PMID:Roles of IL-4 and IL-12 in the development of lupus in NZB/W F1 mice. 901 93

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

The human TNF genes are located within the MHC class-III region on chromosome 6. The presence or absence of an Nco-I restriction site in the 5' non-coding sequence of the TNF beta gene defines two alleles (TNFB*1 and TNFB*2). The segregation of these alleles has been associated with levels of TNF alpha or TNF beta production in systemic lupus erythematosis (SLE), insulin-dependent diabetes mellitus (IDDM) and in healthy control individuals. Rheumatoid arthritis (RA) is characterized by high levels of TNF alpha within the synovial fluid and to address the question of whether this could be brought about by a genetic predisposition to high TNF production by RA individuals, we examined the distribution of this Nco-I polymorphism in 98 healthy volunteers and 123 patients with active rheumatoid arthritis. No difference was observed between the normal and RA groups with respect to haplotype segregation or allelic frequency. Furthermore, no difference was observed between DR4+ or DR4- individuals in the control or RA groups. These data demonstrate that the high level of TNF alpha seen in the joints of RA patients is unlikely to be due to a genetic predisposition of these patients to high TNF alpha production, as defined by the TNF Nco-I restriction fragment length polymorphism (RFLP).
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PMID:TNF Nco-I RFLP is not an independent risk factor in rheumatoid arthritis. 909 56

TNFa, TNFb and TNFc microsatellites were analyzed in 102 SLE patients recruited from a defined area in Southern Sweden. Furthermore we studied 27 SLE patients belonging to 10 multiplex families in which a majority of the members were living within the same area in Southern Sweden. As a control population 98 healthy blood donors from the same region was used. The TNFa2 allele was found more often in the SLE patients (48%) than in the normal controls (33%) (P < 0.01). A low frequency of the TNFa4 allele (10%) vs 16% in controls was observed. The family study showed that the TNFabc haplotype 2-3-1 was more common in SLE associated haplotypes than in non-SLE haplotypes (P < 0.001). The 2-3-1 haplotype was associated with the extended haplotype MHC haplotype [HLA-B8,SC01,DR17]. The results suggest that TNF haplotypes do not constitute special markers of susceptibility to SLE but reflect the increased frequencies of specific intact haplotypes already known to be associated with the disease.
Lupus 1996 Dec
PMID:TNF microsatellites in systemic lupus erythematosus-a high frequency of the TNFabc 2-3-1 haplotype in multicase SLE families. 911 7

The endothelial hybridoma (EAhy926) cell line was employed to clarify whether antiphospholipid antibodies (aPA) [lupus anticoagulant (LA), antiprothrombin antibody (aPT) and/or anticardiolipin antibody (aCL)] and anti-endothelial cell antibodies (AECA) are identical, and establish whether beta2-glycoprotein I (beta2-GPI) is needed for reactivity of aPA to endothelial cells. Ig-G AECA was positive in 9/30 SLE patients with aPA (30.0%) and 10/22 SLE patients negative for aPA (45.5%). Ig-M AECA was positive in one SLE patient with aPA and one SLE patient without aPA. AECA-positivity was not significantly different among unfixed, TNF-stimulated and fixed EAhy926. The influence of beta2-GPI on the reactivity of serum to EAhy926 was minimal, and absorption experiments of serum with cardiolipin-liposome/beta2-GPI or phosphatidylserine-liposome/prothrombin gave little evidence of cross-reactivity of aPA and AECA. The results of our study suggest that aPA and AECA may have partially cross-reacted, but were different antibodies. However, further study is needed to clarify the clinico-pathological significance of AECA.
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PMID:Anti-endothelial cell antibodies to the endothelial hybridoma cell line (EAhy926) in systemic lupus erythematosus patients with antiphospholipid antibodies. 913 70

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by polyclonal B cell activation and by the production of anti-double-stranded (ds) DNA antibodies. Given the inhibitory effects of IL-12 on humoral immune responses, we investigated whether IL-12 displayed such an activity on in vitro immunoglobulin production by SLE PBMC. Spontaneous IgG, IgG1, IgG2, IgG3 and IgM antibody production was dramatically reduced by addition of IL-12. These results were confirmed by Elispot assays detecting IgG- and anti-dsDNA-secreting cells. While IL-6 and TNF titres measured in PBMC supernatants were not modified by addition of IL-12, interferon-gamma (IFN-gamma) titres were up-regulated and IL-10 production down-regulated. Since addition of IFN-gamma did not down-regulate immunoglobulin production and since the inhibitory activity of IL-12 on immunoglobulin synthesis was not suppressed by anti-IFN-gamma antibody, we concluded that the effect of IL-12 on immunoglobulin production was not mediated through IFN-gamma. Our data also argue against the possibility that down-regulation of endogenous IL-10 production was responsible for the effect of IL-12. Thus, inhibition of IL-10 production by IFN-gamma was not accompanied by inhibition of immunoglobulin production, and conversely, restoration of IL-10 production by anti-IFN-gamma antibody did not suppress the inhibitory activity exerted by IL-12 on immunoglobulin production. Taken together, our data indicate that reduction of excessive immunoglobulin and anti-dsDNA antibody production by lupus PBMC can be achieved in vitro by IL-12, independently of IFN-gamma and IL-10 modulation.
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PMID:IL-12 inhibits in vitro immunoglobulin production by human lupus peripheral blood mononuclear cells (PBMC). 915 13

Low TNF production and its association with TNF gene restriction fragment length polymorphism (RFLP) was demonstrated in (NZW/NZB) F1 mice. However, little is known about the significance of TNF production in association with TNF gene polymorphism in human SLE. This study was designed to evaluate the role of TNF production of peripheral blood mononuclear cells (PBMC) and its association with TNFB gene polymorphism in SLE, particularly lupus nephritis. TNFB gene polymorphism was defined by PCR-NcoI RFLP. TNF productions of phytohemagglutinin (PHA)-stimulated PBMC and T cells were examined by bioassay using L929 cell line and ELISA. The PBMC stimulated by PHA from patients with SLE (n = 60) tended to secrete less amounts of TNF by bioassay (1032 +/- 184 pg/ml vs 1524 +/- 224 pg/ml, P = 0.094), and TNF-beta by ELISA (P = 0.0082) than that from normal controls (n = 38). The low TNF-alpha producer was more frequent in nephritis than non-nephritis (34.4% vs 7.1% respectively, P < 0.01). TNF-beta also revealed similar results (53.1% vs 21.4%, P < 0.05). In SLE, mean production of TNF-beta was decreased in TNFB*2 homozygote (n = 18) than that in TNFB*1 homozygote (n = 9) (1126.3 +/- 145 pg/ml) vs 642 +/- 118.4 pg/ml, respectively, P = 0.021), whereas TNF-alpha production showed little difference between the two groups (710.1 +/- 56.4 vs 542.4 +/- 71.1 pg/ml, respectively, P = 0.149). Our results demonstrate that decreased TNF production of PBMC, which was significantly associated with TNFB*2 homozygosity, could be an important predisposing factor of lupus nephritis in Koreans.
Lupus 1997
PMID:Decreased tumour necrosis factor-beta production in TNFB*2 homozygote: an important predisposing factor of lupus nephritis in Koreans. 930 64


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