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)

The effect of hydrocortisone (HC) has been investigated on PWM and LPS-induced immunoglobulin (Ig) production by blood mononuclear leucocytes (MNL) from normal donors and patients with systemic lupus erythematosus (SLE). In the absence of HC, PWM stimulated Ig production in normal but not in SLE cells. In the presence of HC, the normal PWM response was greatly enhanced and a strong response was now seen in SLE. Spontaneous Ig production, which was higher for SLE-MNL, was not greatly affected by HC. A response to LPS was observed in both normal and SLE-MNL in the absence of HC and HC was now inhibitory, confirming that the mode of action of the 2 mitogens is different. It seems likely that HC acts by suppressing cells which influence mitogen responses, and the possibility that the principal target, at least in SLE-MNL, is the monocyte is discussed. The stimulatory effect of HC could be useful in the study of antigen-induced Ig production in SLE.
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PMID:The effect of hydrocortisone on PWM and LPS-induced immunoglobulin production in blood leucocytes from patients with systemic lupus erythematosus. 666 7

The bone marrow granulocyte-macrophage progenitor cells (CFU-C) in patients with systemic lupus erythematosus (SLE) were estimated according to the double-layer soft agar system of Pike and Robinson. When nucleated narrow cells from patients with SLE were cultured with peripheral leukocytes from normal donors as a source on colony stimulating activity (CSA), colony counts (the term colony indicating aggregates of more than 50 cells) in active SLE were reduced significantly but cluster counts (cluster: 10 to 50 cells) were divided into two groups of markedly increased and decreased clusters. When normal nucleated marrow cells were cocultured in the overlayer with peripheral leukocytes of patients with SLE in he feeder layer, colony counts decrease significantly but cluster counts remained within the normal range. When CFU-C by normal nucleated marrow cells were studied in the presence of PHA- or LPS-induced CSA of peripheral leukocytes from patients with SLE, total colony and cluster counts decreased. These data indicate the granulomonocytopenia in SLE may result from the diminution of production of CSA in peripheral leukocytes and/or the direct impairment of growth and differentiation in progenitor cells of granulocytes and macrophages.
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PMID:Colony forming units in culture and colony stimulating activity of systemic lupus erythematosus. 697 21

We have succeeded in generating B cell colonies from freshly separated human peripheral blood by the double agar layer technique and expanding them in liquid culture for several weeks. Populations of cells enriched in B cells were placed into the upper layer with or without bacterial LPS. Although B cell colonies were observed without LPS, the addition of LPS to the cells in the upper agar layer increased the number of colonies. Also necessary for optimal B cell colony formation was the presence in the lower agar layer of either culture supernatant of PHA-stimulated mononuclear cells or purified T cells and PHA. Without such helper factors in the lower layer, only a few B cell colonies were observed in the upper layer. By using these techniques, peripheral blood lymphocytes from normal individuals and patients with active systemic lupus erythematosus (SLE) were studied for the generation of B cell colonies. Significantly more B cell colonies were observed in patients with SLE, using either kind of "helper" factor. In addition, T cells from normal individuals and patients were tested for their ability to help B cell colony formation. The SLE T cells were found to be defective in this function relative to normal T cells. Thus, although patients with SLE were hyperactive in forming B cell colonies, thier T cells were defective in supporting the formation of B cell colonies from normal individuals.
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PMID:Defective regulation of B lymphocyte colony formation in patients with systemic lupus erythematosus. 697 74

Disturbances in suppressor cell function have been considered important in the pathogenesis of systemic lupus erythematosus (SLE), a conclusion supported by studies with New Zealand mice. To determine whether other SLE mice display similar immunoregulatory defects, we investigated the susceptibility of autoimmune MRL mice to unresponsiveness induced by hapten-modified self (HMS). The response of splenocytes from MRL-lpr/lpr mice (lpr) was compared with those of sex- and age-matched, congenic MRL-+/+ mice (+/+), and H-2-identical (H-2k) CBA/J mice. Spleen cells (NSC) were cultured in vitro with hapten-modified syngeneic splenocytes (TNP-SC) and tested for responsiveness to TNP-LPS (for tolerance) or their ability to suppress the response of fresh cells. There was no difference in the susceptibility of lpr splenocytes from 3- and 10-mo-old mice to the induction of tolerance or suppression when compared with those from age-matched +/+ or CBA mice. To evaluate any quantitative defects in the responsiveness of lpr splenocytes to HMS, we modified the conditions under which suppressor activity was generated. Varying the ratio of NSC to TNP-SC from 10:1 to 2000:1, or changing the concentration of TNBS for haptenation from 10 mM to 0.5 mM per 10(8) spleen cells revealed no differences in the dose-response curves of lpr splenocytes for both tolerance and suppression when compared with those of the CBA. These results indicate that clinically affected MRL mice have intact suppressor cell activity in response to antigen-modified self and suggest a possible therapeutic role of this modality in inducing tolerance to self-antigens.
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PMID:The induction of tolerance and suppression in autoimmune MRL mice using hapten-modified self. 725 56

The onset of clinical disease in autoimmune MRL-lpr/lpr mice is preceded by a switch from predominantly IgM production to IgG production. Previous studies have shown that IgG autoantibodies play a central role in the development of life-threatening glomerulonephritis in this strain. Delaying or preventing the switch from IgM to IgG production might therefore be of therapeutic benefit. We previously documented similarities in the B cell repertoire expressed by young MRL-lpr/lpr mice and normal mice treated with the polyclonal activator LPS. Recent in vivo studies indicate that cross-linking membrane IgM or IgD can suppress LPS-dependent IgG production in normal animals. These observations led us to examine whether membrane cross-linking could also lower serum IgG levels in MRL-lpr/lpr mice. Lupus-prone animals were treated with multivalent anti-IgD conjugated to high m.w. dextran. This anti-IgD dextran conjugate was previously shown to reduce IgG production in LPS-stimulated normal animals. Treatment of young lupus-prone MRL-lpr/lpr mice resulted in a significant reduction in the total number of B cells secreting IgG and lower serum titers of IgG anti-DNA and IgG anti-histone autoantibodies. Anti-IgD dextran treatment also delayed the development of glomerulonephritis and improved survival. Thus, anti-IgD dextran interfered with autoantibody-dependent disease progression, perhaps by inhibiting the switch from IgM to IgG autoantibody production.
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PMID:Treatment with dextran-conjugated anti-IgD delays the development of autoimmunity in MRL-lpr/lpr mice. 751 19

Interleukin-1 receptor antagonist (IL-1ra) binds competitively to IL-1 receptors but does not transduce the signal which blocks the biological activities induced by IL-1. In this study, polymorphonuclear neutrophils (PMN) and mononuclear cells (MNC) from the patients with active systemic lupus erythematosus (SLE) (n = 11), inactive SLE (n = 13) and normal individuals (n = 13) were compared for the IL-1ra producing capacity of these cells. PMN and MNC at a concentration of 1 x 10(6) cells/ml were incubated with medium alone (spontaneous) or stimulated with lipopolysaccharide (LPS, 100 ng/ml) for 24 h. The IL-1ra concentration in the supernatants was quantified by ELISA method. Both spontaneous and LPS-stimulated production of IL-1ra by PMN, but not by MNC, of active SLE were significantly lower than that of inactive SLE or normal groups. Prednisolone (1 and 5 micrograms/ml) did not change the production of IL-1ra by normal PMN either spontaneously or LPS-stimulation in in vitro study. Moreover, the IL-1ra producing capacity of PMN in seven active SLE on admission and after intensive immunosuppressive treatment was measured. These results suggest that the defective IL-1ra production by SLE-PMN is relevant to disease activity and may be regarded as a new indicator of disease activity in patients with active SLE.
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PMID:Defective spontaneous and bacterial lipopolysaccharide-stimulated production of interleukin-1 receptor antagonist by polymorphonuclear neutrophils of patients with active systemic lupus erythematosus. 770 55

MRL-lpr/lpr mice develop an autoimmune disease similar to human systemic lupus erythematosus (SLE). The main characteristics of this disease are increasing autoantibody formation, elevated plasma levels of immune complexes, a massive lymphoproliferation, a rising proteinuria, and arthritic symptoms. Finally, the mice die at an age of about 6 months due to a fatal immune complex glomerulonephritis. Macrophages are involved in the development of SLE due to their functions as antigen-presenting as well as cytokine-producing cells. T and B cells are involved in the disease by secreting cytokines and producing antibodies. Pentoxifylline (PTX), a xanthine derivative, is known to exert different effects on functions of leukocytes and erythrocytes and has been used in clinical studies, e.g., in septic shock syndrome. In our studies we first investigated the in vitro effect of PTX on macrophages and lymphocytes derived from MRL-lpr mice. Our investigations concerning production of superoxide anion and TNF-alpha by LPS and/or IFN-gamma activated bone marrow and peritoneal macrophages, MHC class II expression on these cells, and the proliferative capacity and Il-2 production of mitogen activated lymphocytes, revealed that PTX reduces the activation and the inflammatory response of these cells. Based on these results, we further investigated the effect of in vivo treatment with PTX. MRL-lpr mice treated with PTX showed diminished proteinuria, reduced titer of dsDNA-autoantibodies in the plasma and an increased survival rate. Our data clearly demonstrate that PTX is able to diminish the severity of the disease and to prolong the life of MRL-lpr/lpr mice.
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PMID:In vitro and in vivo effects of pentoxifylline on macrophages and lymphocytes derived from autoimmune MRL-lpr/lpr mice. 785 38

The monoclonal nonspecific suppressor factor (MNSF) is a lymphokine produced by a murine T cell hybridoma capable of suppressing Ab production by LPS-stimulated B cells. The existence of a human counterpart of MNSF, designated as the human nonspecific suppressor factor (hNSF), was likely because the anti-MNSF mAb (MO6) recognizes a similar suppressive activity in supernatants of Con A-stimulated human PBMC. By using the MO6 mAb, we investigated the presence of hNSF in the ascitic fluid of a patient with SLE. A small amount of cross-reactive hNSF was isolated from concentrated ascitic fluid fractionated with the MO6-affinity column, and a specific anti-hNSF mAb (P2) was produced. The hNSF eluted from the P2-affinity column could suppress up to 80% of the PWM-induced IgG production of human PBMC in a dose-dependent manner, even when added in late culture periods. Moreover, hNSF could inhibit proliferation of PBMC triggered by either PWM or Con A, which also implies an effect on T cells. On SDS-PAGE, the isolated hNSF resolved as a single peak of about 66 kDa and probably represents an aggregate of hydrophobic subunits. On reverse-phase HPLC, the bioactivity could be recovered from a single peak at 18.3 min. The suppression of IgG production induced by hNSF could be partly neutralized by preincubation with an anti-TCR-alpha mAb, whereas an anti-TCR-beta did not have any effect. Anti-TCR-alpha could also directly bind to the isolated nNSF, demonstrating some serologic relationship, as has been reported for several Ag-specific suppressor systems.
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PMID:Isolation and characterization of a human nonspecific suppressor factor from ascitic fluid of systemic lupus erythematosus. Evidence for a human counterpart of the monoclonal nonspecific suppressor factor and relationship to the T cell receptor alpha-chain. 813 68

Thymulin is a nonapeptide hormone isolated from the thymus gland. It has immunomodulatory effects which have not yet been well defined. Its major actions have been shown to be on T-cells and their immature precursors. In this study, thymulin was tested in vitro for its effect on the release of IL-1 alpha, IL-2, IL-6 and TNF alpha from peripheral blood mononuclear cells (PBMC) obtained from normal volunteers and patients with active systemic lupus erythematosus (SLE). In our experiments, PBMC (stimulated with LPS or PHA) were cultured for 24 h in the presence of 1,100 or 1,000 ng/ml of thymulin. Supernatants were subsequently assayed for cytokine activities using commercially available ELISA (IL-2, IL-6 and TNF alpha) and RIA (IL-1 alpha) kits. Thymulin (1 ng/ml) resulted in a significant (p < 0.01) increase in IL-1 alpha in the volunteers and a significant (p < 0.05) inhibition of this cytokine at all dose levels tested in SLE patients, whose basal levels of IL-1 alpha were significantly (p < 0.05) higher. Thymulin significantly (p < 0.05) inhibited IL-2 only in SLE patients at 1,000 ng/ml. At all dose levels tested, thymulin significantly (p < 0.01) inhibited IL-6 in volunteers, and, only at 1,000 ng/ml, it significantly (p < 0.05) inhibited it in patients with SLE. At the 1,000 ng/ml dose level, TNF alpha was significantly (p < 0.05) inhibited in both volunteers and SLE patients, whose basal levels of this cytokine were significantly (p < 0.05) higher.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thymulin modulates cytokine release by peripheral blood mononuclear cells: a comparison between healthy volunteers and patients with systemic lupus erythematosus. 850 50

Acebutolol induces transient polyclonal B cell activation in C57B1/6 mice but down-modulates the spontaneous polyclonal activation of NZBxNZW lupus mice. The immunomodulatory effects of this beta-blocker were studied in C57l/6 mice injected with LPS or immunized with sheep red blood cells. The effect of acebutolol on the polyclonal activation of lymphocytes induced by LPS was also investigated in heterozygous and nu/nu C57BL/6 mice. Finally, the direct effect of acebutolol on spleen cells was studied in vitro. Acebutolol treatment for 15 days (50mg/kg/day) inhibited the polyclonal activation of lymphocytes induced by LPS in C57BL/6 and in C57BI/6 nu/nu mice, but increased the humoral response to sheep red blood cells in C57Bl/6 mice. Moreover, spleen cells from C57Bl/6 mice treated for 15 days with acebutolol showed an increased number of CD5+ and CD4+ lymphocytes, as well as an increased reactivity to concanavalin A but not to LPS. In vitro, acebutolol at 10(-5)-10(-7) M induced an increased reactivity of spleen cells from naive mice to concanavalin A, whereas it did not affect the B cell responsiveness to LPS. These results indicate that acebutolol modulates both T-cells and non T-cells in the immune system.
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PMID:Evidence for a dual effect of acebutolol, a beta blocker, on the mouse humoral immune response. 857 44


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