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 dietary dehydroisoandrosterone (DHA) on several immunological abnormalities associated with the development of systemic lupus erythematosus in New Zealand Black/New Zealand White F1 (NZB/W) female mice was examined. Despite the extraordinary benefits in prolonged survival and decreased synthesis of antibodies to double-stranded DNA obtained by adding DHA (0.4% w/v) to the diet fed to these mice (Lucas et al. (1985) J. Clin. Invest. 75, 2091-2093), remarkably small changes in the chemistry and function of the immune system were detected. DHA prevented the increases in spleen mass and in peritoneal cell number which occur with age in NZB/W female mice, but did not prevent the development of hypergammaglobulinemia. DHA did not affect peritoneal macrophage functions as measured by the phagocytosis of opsonized and non-opsonized sheep erythrocytes, or the zymosan-stimulated release of PGE2, 6-ketoPGF1 alpha, TXB2 and LTC4. In spleen, DHA delayed the loss of T-cell mitogenic responses until 5.5 months of age, but did not alter the spleen lymphocyte population.
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PMID:Dehydroisoandrosterone prevention of autoimmune disease in NZB/W F1 mice: lack of an effect on associated immunological abnormalities. 252 78

We report here on interleukin-2 (IL-2) suppressive factors, synovial fluid (SF) peripheral blood mononuclear cells (PBM), derived from short term cultures of unstimulated PBM of patients with systemic lupus erythematosus (SLE). SF PBM suppressed production of IL-2, but not proliferative responses to this lymphokine. It was sensitive to acid (pH 2.6), heat (56 degrees C), and tryptic digestion. It retained activity in the presence of 2-mercaptoethanol (2-ME), had no interferon activity and no non-specific cytotoxicity. Although crude SF PBM contained IgG and PGE2, these were not associated with its 2 active fractions. SF PBM was partially purified on a G-200 Sephadex column. IL-2 suppressive activity was detected in 2 fractions of molecular weights corresponding to greater than 150 kD and 40-60 kD, the latter acting only in the presence of monocytes. SF PBM appear to affect directly the IL-2 producer cell, since it suppressed IL-2 production by (1) mitogen stimulated PBM depleted of CD8+ suppressor cells and by (2) mitogen induced Jurkat cells. These "spontaneous" suppressive factors were ubiquitous in SLE, and may be important tools for studying the defective IL-2 production in SLE and its significance in the development of the disease.
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PMID:Partial purification and characterization of systemic lupus erythematosus derived factors that suppress production of interleukin-2. 326 62

Highly purified and cloned preparations of interleukin-1 (IL-1) were found to antagonize the capacity of erythropoietin (Epo) to stimulate the proliferation of mouse spleen and bone marrow erythroid precursor cells (EPC) in culture. Cloned murine IL-1 and purified and cloned human IL-1 alpha and IL-1 beta were approximately equipotent in this assay. IL-1 inhibited the proliferation response of EPC even when added as long as 17 h after Epo, suggesting that IL-1 does not affect binding of Epo to receptors or biochemical events following shortly thereafter. Indomethacin did not influence the inhibitory effect of IL-1 on Epo-induced proliferation, and PGE2 had no demonstrable effect on the process. Tumor-necrosis factor-alpha and interferons beta 1, and gamma did not affect Epo-induced proliferation. It is suggested that IL-1 mediated antagonism of the effects of Epo on erythroid precursors is a factor in the pathogenesis of many types of hypoplastic anaemia, including those associated with infections, rheumatoid arthritis and systemic lupus erythematosus, giant-cell arteritis, graft-versus-host disease and disorders associated with lymphocyte-mediated suppression of erythropoiesis.
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PMID:Inhibition by interleukin-1 of the action of erythropoietin on erythroid precursors and its possible role in the pathogenesis of hypoplastic anaemias. 349 70

Previous studies have shown that resident peritoneal macrophages from mice with systemic lupus erythematosus (SLE) show defective Fc-mediated phagocytosis and binding of opsonized sheep erythrocytes (EA) in vitro. Possible causes of this defect in (NZB X NZW)F1 (B/W) mice were investigated. These included a maturational block in peritoneal macrophage differentiation, the production by peritoneal cells of a factor which inhibits Fc receptor expression and phagocytosis, and an abnormal response by macrophages of autoimmune mice to prostaglandins. Resident peritoneal macrophages of B/W mice did not show a maturational block since incubation with either (a) differentiating agents such as 4 beta-phorbol 12 beta-myristate 13 alpha acetate or retinoic acid, or (b) lymphokine (LK), prepared by Con A stimulation of mouse spleen cells, failed to enhance Fc-mediated phagocytosis and binding by B/W cells relative to controls. However, LK from B/W and B6AF1 cells stimulated Fc-mediated phagocytosis and binding by bone-marrow (BM)-derived macrophages of CBA/H mice; B/W LK also stimulated BM cells from B/W mice. Peritoneal cell supernatants did not inhibit phagocytosis of Fc receptor expression by BM-derived macrophages in vitro. Prostaglandin E treatment of peritoneal or BM-derived macrophages in vitro failed to restore decreased phagocytosis and binding of EA induced by culture in indomethacin and failed to stimulate phagocytosis by untreated cultures. The reason for the observed defect remains obscure.
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PMID:Studies of macrophage function in murine systemic lupus erythematosus. 4. Failure to reverse the defect in Fc-mediated phagocytosis and binding by in vitro stimulants or prostaglandins. 372 34

We have examined the urinary excretion of stable immunoreactive eicosanoids in 23 female patients with systemic lupus erythematosus (SLE), 16 patients with chronic glomerular disease (CGD), and 20 healthy women. SLE patients had significantly higher urinary thromboxane B2 (TXB2) and prostaglandin (PG) E2 excretion and significantly lower 6-keto-PGF1 alpha than did healthy women. In contrast, CGD patients only differed from controls for having reduced 6-keto-PGF1 alpha excretion. The group of SLE patients with active renal lesions differed significantly from the group with inactive lesions for having a lower creatinine clearance and urinary 6-keto-PGF1 alpha and higher urinary TXB2. Higher urinary TXB2 excretion was associated with comparable platelet TXB2 production in whole blood, undetectable TXB2 in peripheral venous blood, and unchanged urinary excretion of 2,3-dinor-TXB2. A significant inverse correlation was found between urinary TXB2 and creatinine clearance rate (CCr). In contrast, the urinary excretion of 6-keto-PGF1 alpha showed a significant linear correlation with both CCr and para-aminohippurate clearance rate (CPAH). In four SLE and seven CGD patients, inhibition of renal cyclooxygenase activity by ibuprofen was associated with a significant reduction in urinary 6-keto-PGF1 alpha and TXB2 and in both CCr and CPAH. However, the average decrease in both clearances was 50% lower in SLE patients than in CGD patients, when fractionated by the reduction in urinary 6-keto-PGF1 alpha or PGE2 excretion. We conclude that the intrarenal synthesis of PGI2 and TXA2 is specifically altered in SLE. Such biochemical alterations are associated with changes in glomerular hemodynamics and may play a role in the progression of SLE nephropathy.
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PMID:Functional significance of renal prostacyclin and thromboxane A2 production in patients with systemic lupus erythematosus. 390 Jan 32

Peripheral blood monocytes from 10 systemic lupus erythematosus (SLE) and 10 rheumatoid arthritis (RA) patients as well as from 24 controls were studied for such functions as phagocytosis, bactericidal capacity, iodination, and PGE2 production. Phagocytosis of opsonized erythrocytes, exploring only the Fc receptor, was increased in SLE and RA. Killing of Staphylococcus aureus was decreased in both SLE and RA in the presence of AB serum, but not in the presence of autologous serum. Iodination was, on the average, normal in SLE and elevated in RA. Prostaglandin E2 production was decreased in SLE (except with the highest concentration of Con A) and increased in RA. In SLE, functional alterations were more pronounced in clinically active than in inactive disease. These results show that in SLE and RA peripheral blood monocytes have alterations of their functions that are independent of serum factors. It is suggested that these abnormalities may be relevant to the pathogenetic mechanisms and evolution of these diseases.
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PMID:Phagocytosis, bactericidal capacity, and PGE2 production of monocytes in systemic lupus erythematosus and rheumatoid arthritis. 659 49

Glomerular filtration rate (GFR; 51Cr-EDTA clearance), serum creatinine concentration and urinary excretion of prostaglandins were measured in 8 patients with systemic lupus erythematosus (SLE) before and after 2 weeks of treatment with acetylsalicylic acid (ASA). ASA 65 mg/kg or up to 4 g/daily was given as a sustained release preparation. The serum salicylate concentration ranged from 0.3 to 1.6 mmol/l. Serum creatinine after 1 and 2 weeks and GFR after 2 weeks of ASA treatment showed no significant changes. There was a clearcut decrease in urinary excretion of prostaglandins PGE2 and PGF2 alpha, by 44% and 50%, respectively. It is concluded that therapeutic doses of ASA do not cause deterioration of GFR in patients with SLE and normal or moderately reduced renal function.
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PMID:Effect of acetylsalicylic acid on renal function in systemic lupus erythematosus. 716 Apr 18

MRL-lpr/lpr mice spontaneously develop an autoimmune disease with nephritis similar to human systemic lupus erythematosus. In these animals, treatment with E-series prostaglandins ameliorates renal disease and prolongs survival, perhaps by modulating production of cytokines or eicosanoids. To further define the mechanisms of action of E-series prostaglandins in established murine lupus nephritis, we administered the prostaglandin E1 (PGE1) analog misoprostol to 20-week-old MRL-lpr/lpr mice by twice-daily subcutaneous injection. After 2 days of treatment, misoprostol reduced renal cortical interleukin-1 beta (IL-1 beta) mRNA levels compared to vehicle-treated controls (0.19 +/- 0.06 (misoprostol) vs 0.50 +/- 0.04 (vehicle) densitometry units; P < 0.005). A similar reduction in cortical IL-1 beta mRNA levels was found in left kidneys harvested from MRL-lpr/lpr mice following 2 days of treatment with misoprostol compared to right kidneys harvested from the same animal prior to the first dose of PGE1 analog (0.12 +/- .05 (left) vs 0.39 +/- 0.18 (right) densitometry units; P < 0.05). This reduction in cortical IL-1 beta mRNA levels was not associated with alterations in renal production of thromboxane B2, PGE2, or leukotriene B4 or with significant changes in the severity of renal inflammatory cell infiltrates. Time-course studies indicated that IL-1 beta mRNA levels were decreased within 24 hr of initiating misoprostol therapy. This reduction in IL-1 beta mRNA levels was transient because levels were not reduced after 1 week of treatment with the PGE1 analog.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of short-term treatment with the prostaglandin E1 (PGE1) analog misoprostol on inflammatory mediator production in murine lupus nephritis. 770 69

Studies from our laboratory indicate that n-3 (fish oil, FO) lipids at 10% (w/w) in a nutritionally adequate, semipurified diet, and supplemented with equal levels of antioxidants, extended the life span of lupus-prone (NZB/NZW)F1 (B/W) female mice as compared to n-6 (corn oil, CO) lipids. The early rise of autoimmune disease in CO-fed mice was closely linked to the loss of T-cell function. Both IL-2 production and IL-2 receptor expression were reduced due to the loss of naive T-cells and a rise in memory T-cells. Proliferative response to both mitogens and superantigens (staphylococcal enterotoxins A and B) was higher in FO-fed 6.5-mon-old mice. These changes paralleled decreased PGE2 production by splenic cells from FO-fed mice. Analysis of mRNA expression in different organs revealed differential effects of dietary lipids. In FO-fed mice, transforming growth factor beta 1 (TGF beta 1) expression was decreased in kidneys, but splenic tissues had higher expression of TGF beta mRNA. As TGF beta promotes programmed cell death (PCD), we studied the effects of CO and FO on PCD rates in lymphocytes. Both propidium iodide staining and DNA fragmentation were elevated in lymphocytes of FO-fed mice when compared to CO-fed mice of similar age. Also, increased PCD correlated closely with increased Fas gene expression. Thus, in addition to various other antiinflammatory effects, dietary FO appears to increase PCD and prevent accumulation of self-reactive immune cells in lymphoid organs. Further studies are required to dissect the pro- and antiinflammatory mechanisms associated with dietary n-3 and n-6 lipids in modulating autoimmune disorders or malignancy during aging.
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PMID:Modulation of antioxidant enzymes and programmed cell death by n-3 fatty acids. 872 1

Abnormalities of prostanoid metabolism, which may affect renal function, were studied in lupus nephritis. The subjects were 31 patients with lupus nephritis, ten with non-renal SLE, and four with renal, non-SLE collagen disease. Urinary levels of various prostanoids, thromboxane B2(TXB2), 11-dehydro-TXB2, 6-keto-PGF1 alpha,2,3-dinor-6-keto-PGF1 alpha and PGE2, and plasma level of 11-dehydro-TXB2, were determined. The effects of four days' dosing of a selective thromboxane A2 (TXA2) synthetase inhibitor, DP-1904 (DP), on prostanoid metabolism, were also studied. Urinary excretion of TXB2, which reflects the renal production of TXA2, was significantly increased in patients with lupus nephritis as compared with non-renal SLE (p < 0.05). The urinary TXB2/6-keto-PGF1 alpha ratio was also increased in lupus nephritis as compared with non-renal SLE or healthy controls (p < 0.01), indicating a prostanoid imbalance, which may lead to impaired renal function and subsequent pathology. The urinary TXB2/6-keto-PGF1 alpha ratio in these lupus nephritis patients showed negative correlations with Ccr and positive correlations with anti-DNA antibody titer (p < 0.001). DP was administered orally (400 mg/day, given in two divided doses) for four days to eight lupus nephritis patients. The urinary excretion of TXB2 and urinary TXB2/6-keto-PGF1 alpha ratio were decreased after one to two days of treatment in all patients. An increase in creatinine clearance used as a measure of renal function was observed in four of eight patients. Furthermore, no side effects were elicited during the four days of treatment. The conclusion reached were that the abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function through hemodynamic mediation, and that the deviated metabolism was reversible and, at least partially, corrected by a TXA2 synthetase inhibitor.
Lupus 1996 Apr
PMID:Abnormal prostanoid metabolism in lupus nephritis and the effects of a thromboxane A2 synthetase inhibitor, DP-1904. 874 26


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