thromboxane-b2 and Lupus-Erythematosus--Systemic

All pregnancy-associated tissues are capable of producing prostaglandins including PGI2 and TXA2. In normal pregnancy there is a dominance of PGI2 over TXA2 which may contribute to the maternal circulatory adaptation to pregnancy. Furthermore, both fetoplacental PGI2 and TXA2 production are important regulators of the fetal blood supply. It has been clearly established that in pre-eclampsia PGI2 production decreases in the fetoplacental tissues and quite probably also in the maternal tissues. The effect of this change may be further exaggerated by the simultaneous stimulation in pre-eclampsia of TXA2 production. The reason for PGI2 deficiency is not known. Other vasoactive agents, such as endothelin, may act in concert with prostaglandins. Relative PGI2 deficiency is likely to exist also in IUGR and lupus anticoagulant syndrome of pregnancy. In the latter, lupus anticoagulant may directly inhibit the synthesis of PGI2. One study suggests PGI2 deficiency also in early pregnancies of women with a history of repeated abortions. Prostaglandin production increases during full-term labour, and similar but smaller changes also occur in preterm labour. A silent bacterial infection may trigger the onset of preterm labour through cytokine-stimulated increase of prostaglandin production. No data were found on prostaglandin production in post-term pregnancies. That oligo-polyhydramnios is possibly prostaglandin mediated is suggested by the control of polyhydramnios by indomethacin treatment. Smoking decreases the production of PGI2 and possibly increases that of TXA2, which may lead to decreased blood flow and IUGR. Which constituent of cigarette smoke exerts this effect is not known. Ethanol consumption causes aberrations in prostaglandin metabolism which cannot be directly connected with fetal alcohol effects.

Topics: Abortion, Habitual; Alcohol Drinking; Epoprostenol; Female; Fetal Growth Retardation; Humans; Lupus Erythematosus, Systemic; Obstetric Labor, Premature; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Prostaglandins; Smoking; Thromboxane A2; Thromboxane B2

Low-dose aspirin prevents platelet aggregation by suppressing thromboxane A2 (TXA2 ) synthesis. However, in some individuals TXA2 suppression by aspirin is impaired, indicating suboptimal inhibition of platelet cyclooxygenase 1 (COX-1) by aspirin. Because patients with systemic lupus erythematosus (SLE) have increased risk of thrombotic events, many receive aspirin; however, the efficacy of aspirin in SLE has not been determined. We examined the hypothesis that aspirin response is impaired in SLE.. We assessed the effect of aspirin by measuring concentrations of the stable metabolite of TXA2 , serum thromboxane B2 (sTXB2 ), before and after treatment with daily aspirin (81 mg) for 7 days in 34 patients with SLE and 36 control subjects. The inability to suppress sTXB2 synthesis to <10 ng/ml represents suboptimal inhibition of platelet COX-1 by aspirin.. Aspirin almost completely suppressed sTXB2 in control subjects to median 1.5 ng/ml (interquartile range [IQR] 0.8-2.7) but had less effect in patients with SLE (median 3.1 ng/ml [IQR 2.2-5.3]) (P = 0.002). A suboptimal effect of aspirin was present in 15% (5 of 34) of the patients with SLE but not in control subjects (0 of 36) (P = 0.023). Incomplete responders were more likely to have metabolic syndrome (P = 0.048), obesity (P = 0.048), and higher concentrations of C-reactive protein (CRP) (P = 0.018).. The pharmacologic effect of aspirin is suboptimal in 15% of patients with SLE but in none of the control subjects, and the suboptimal response was associated with metabolic syndrome, obesity, and higher CRP concentrations.

Topics: Adult; Aspirin; Biomarkers; Blood Platelets; C-Reactive Protein; Chi-Square Distribution; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Female; Humans; Lupus Erythematosus, Systemic; Male; Metabolic Syndrome; Middle Aged; Obesity; Prospective Studies; Thromboxane B2; Time Factors; Treatment Outcome

To evaluate the rate of thromboxane biosynthesis in patients with systemic lupus erythematosus (SLE), exploring the interplay between antiphospholipid antibodies (aPL) and 2 markers of endothelial perturbation: thrombin generation and platelet activation.. A comparison of 11-dehydrothromboxane B2 (TXB2) excretion, which is a marker of in vivo platelet activation, aPL, von Willebrand factor (vWF) and tissue plasminogen activator (tPA), which are 2 circulating markers of endothelial perturbation, and plasma levels of the prothrombin fragment F1+2, which is a marker of thrombin generation, was performed in 40 SLE patients and 40 healthy subjects. Thromboxane metabolite excretion was also measured in 8 SLE patients before and after treatment with low-dose aspirin.. SLE patients had significantly higher 11-dehydro-TXB2 excretion, plasma F1+2, vWF, and tPA levels than controls. A statistically significant correlation was found between plasma levels of vWF and tPA and excretion of thromboxane metabolite. Moreover, significantly higher 11-dehydro-TXB2 was found in patients with aPL positivity and endothelial perturbation. Low-dose aspirin suppressed 11-dehydro-TXB2 by 80%, suggesting a predominant platelet source of enhanced thromboxane biosynthesis. After a median followup of 48 months, all SLE patients who experienced major cardiovascular events had thromboxane metabolite excretion, aPL positivity, and signs of endothelial perturbation.. We have characterized a sensitive marker of platelet activation, which is abnormal in SLE patients who were positive for aPL and endothelial perturbation. This analytical approach may help identify those patients at increased risk of thrombosis as potential candidates for antiplatelet therapy.

Topics: Adult; Antibodies, Antiphospholipid; Antigens; Aspirin; Cross-Sectional Studies; Dose-Response Relationship, Drug; Female; Humans; Ischemia; Lupus Erythematosus, Systemic; Male; Middle Aged; Myocardial Infarction; Stroke; Thromboxane B2; Thromboxanes; Tissue Plasminogen Activator; Venous Thrombosis; von Willebrand Factor

Verify that resistance to aspirin may have an impact on pregnancy and neonatal outcome.. We enrolled 43 pregnant women, aged 30.7 ± 4.0 years regularly taking 75 mg of aspirin daily and 32 (aged 30.8 ± 4 years) pregnant women not receiving aspirin who served as control group. Laboratory tests were performed at 18 to 22 weeks of gestation, 28 to 32 weeks of gestation and 16 to 32 weeks after delivery. Resistance to aspirin was defined as urinary 11-dehydrothromboxane B2 (u11-dTXB2) concentrations in the highest quartile and additionally, as the resistance index (RI) calculated for each woman, defined as the difference between u11-dTXB2 concentration of each woman treated with aspirin and the median value at the same time point measured in the control group.. Women taking aspirin in the highest quartile of u11-dTXB2 delivered prematurely (35.8±3.4 vs 38.1±1.7 weeks, p=0.02). Delivery of small for gestational age (SGA) newborns (p=0.003) as well as fetal distress (p=0.014) and preeclampsia (p=0.003) occured more frequently in aspirin-resistant women. Resistance to aspirin based on the RI value was also associated with higher prevalence of preeclampsia (p=0.02) and SGA newborns delivery (p=0.01). The two groups resistant to ASA designed on the basis of both (RI and u11-dTXB2 urine levels) methods compared with ASA sensitive group differed in frequency of SLE prevalence.. Aspirin resistance may be associated with increased risk of adverse pregnancy outcomes including preeclampsia, premature delivery and delivery of SGA newborns.

Topics: Adult; Aspirin; Cesarean Section; Drug Resistance; Female; Fetal Distress; Humans; Infant, Newborn; Infant, Small for Gestational Age; Lupus Erythematosus, Systemic; Obstetric Labor, Premature; Parity; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Thromboxane B2; Young Adult

Recent studies have shown that patients with antiphospholipid antibodies (aPL) have increased lipid peroxidation. We evaluated the urinary excretion of 11-dehydro thromboxane B2 (11-DH-TXB(2) and isoprostane F(2alpha)III (IPF(2alpha)III), reflecting platelet activation and lipid peroxidation in vivo, and plasma soluble markers of endothelial cell, platelet and blood coagulation activation: soluble vascular cell adhesion molecule-1 (sVCAM-1), P- and E-selectin (sPsel and sEsel), F1 + 2 fragment of prothrombin (F1 + 2), thrombin-antithrombin complexes (TAT) and D-Dimer (DD). We studied 79 patients with aPL (47 with previous thrombosis), 45 healthy volunteers (normal controls, NC), 12 patients with systemic lupus erythematosus (SLE) without aPL and a thrombosis control group (TCG) without thrombophilia (n = 16). Urinary levels (mean, range) of eicosanoids and isoeicosanoids were significantly increased in 39 patients with aPL compared with 25 NC, 11-DH-TXB(2) 164.0 ng/mmol creatinine (9.5-1162.8) versus 43.4 ng/mmol creatinine (4.2-87.6), P < 0.001; IPF(2alpha)III 56.9 pg/mg creatinine (5.5-388.7) versus 27.0 pg/mg creatinine (4.6-87.6), P = 0.03. Both metabolites were significantly correlated (rho = 0.49, P = 0.014), but none correlated with any clinical manifestation or antibody profile. The aPL group presented increased levels of sPsel, sEsel, sVCAM-1, TAT, F1 + 2 and DD, but any soluble marker correlated with IPF2alphaIII. Urinary 11-DH-TXB(2) correlated with sPsel (rho = 0.39, P = 0.04). Compared with SLE controls, the SLE group with aPL had higher levels of F1 + 2. Plasma levels of F1 + 2 and DD were significantly increased and a trend to higher sPsel was found in aPL patients with thrombosis compared with the TCG. Platelet activation, lipid peroxidation and blood coagulation activation seem to be important in the pathophysiology of antiphospholipid syndrome.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Antithrombins; Biomarkers; Blood Coagulation; Case-Control Studies; Chi-Square Distribution; Child; Child, Preschool; E-Selectin; Endothelium, Vascular; Female; Fibrin Fibrinogen Degradation Products; Humans; Isoprostanes; Lipid Peroxidation; Lupus Erythematosus, Systemic; Male; Middle Aged; P-Selectin; Platelet Activation; Prothrombin; Statistics, Nonparametric; Thrombosis; Thromboxane B2; Vascular Cell Adhesion Molecule-1

A typical feature of lupus nephritis is glomerular and interstitial leukocyte infiltration. In search of a serological marker of renal disease activity, we examined prostaglandin endoperoxide synthetase (PGHS) activity in peripheral-blood monocytes isolated from 5 healthy subjects and 11 untreated patients with biopsy-proven lupus nephritis, using radioimmunoassay of prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) released during 24-hour cultures with selective stimuli/inhibitors. Unstimulated basal PGE2 and TxB2 synthesis, reflecting in vivo PGHS activity, was greater in the five patients with active renal involvement (World Health Organization [WHO] classes IVb-c) and the six lupus patients without active disease than in the five healthy subjects (TxB2, 2,643+/-198 [standard error], 2,015+/-190, 1,548+/-295 pg/10(6) cells, respectively). Escherichia coli lipopolysaccharide (LPS; 10 microg/mL) potently induced TxB2 or PGE2 synthesis in healthy controls (+255%+/-76% and +611%+/-190%, +688%+/-234% and +3,189%+/-154%; 4 to 24 hours, respectively), an effect abolished by 5 micromol/L of dexamethasone (DEX) or by 5 micromol/L of the protein synthesis inhibitor cycloheximide (CHX). Responses to LPS were reduced in lupus patients without disease activity and reduced even further in those with active nephritis. This may be related to substrate depletion or feedback functional inhibition of the inducible isoform of PGHS. Our assay may prove useful in the early detection of kidney disease activity in lupus erythematosus.

Topics: Adult; Anti-Inflammatory Agents; Biomarkers; Cells, Cultured; Cycloheximide; Dexamethasone; Dinoprostone; Eicosanoids; Escherichia coli; Feedback; Female; Glucocorticoids; Humans; Isoenzymes; Lipopolysaccharides; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Middle Aged; Monocytes; Prostaglandin-Endoperoxide Synthases; Protein Synthesis Inhibitors; Thromboxane B2

Two murine models of lupus were employed to challenge an hypothesized mechanism by which antiphospholipid antibodies (APLA) might promote thrombosis: altering prostacyclin (PGI2) and thromboxane (TX) production. PGI2 levels in mouse blood and the ex vivo release of PGI2 and TX from mouse kidney were measured. Since APLA have been reported to alter synthesis or activation of several molecules mediating fibrinolysis, murine plasma levels of the fibrin degradation product, D-dimer were also determined. Two murine strains, one prone to spontaneous "lupus-like" illness (MRL-lpr) and related strain (MRL-(+2)), were compared. The assays confirm that MRL-lpr mice have increased anticardiolipin antibody (ACA) and two-fold increased release of TX from renal tissues compared to MRL-(+2) mice. However, these mice have low levels of plasma D-dimer. NIH Swiss mice injected with IgG (containing APLA) from thrombosis-prone lupus patients had high blood ACA titers and D-dimer levels, but both ACA and D-dimer were low or non-detectable in Swiss mice injected with saline or normal IgG. Unlike mice with spontaneous lupus-like illness, healthy mice injected with APLA did not differ from controls with respect to plasma or tissue PGI2 or TX levels. The two murine models of lupus differ, because an altered PGI2-TX ratio is a finding in the chronic murine lupus strain MRL-lpr, but is not seen when APLA are injected into normal mice. It is unlikely that APLA alone has a direct effect on cellular production of eicosanoids in vivo.

Topics: Animals; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Calcimycin; Disease Models, Animal; Eicosanoids; Epoprostenol; Female; Fibrin Fibrinogen Degradation Products; Humans; Immunoglobulin G; Kidney; Lupus Erythematosus, Systemic; Male; Mice; Mice, Inbred Strains; Thrombin; Thromboxane B2

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.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Enzyme Inhibitors; Female; Humans; Imidazoles; Kidney Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Middle Aged; Prostaglandins; Reference Values; Regression Analysis; Tetrahydronaphthalenes; Thromboxane B2; Thromboxane-A Synthase

Polyclonal antibodies to double stranded DNA (dsDNA) purified from pooled serum samples of patients with systemic lupus erythematosus (SLE) exerted cytotoxic effects on cultured rat mesangial cells. At concentrations from 5 to 150 IU/ml, antibodies to dsDNA inhibited the incorporation of thymidine labelled with 3H into rat mesangial cells in a dose response manner after three days of culture. In contrast, normal human IgG (1 mg/ml), heat aggregated human IgG (1 mg/ml), N-formyl-methionyl-leucyl-phenylalanine (1 x 10(-7) mol/l), tumour necrosis factor alpha (16 U/ml), lipopolysaccharides (1 microgram/ml), 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA) (20 ng/ml), interleukin 1 beta (10 U/ml), and 20% v/v phytohaemagglutinin stimulated mononuclear cell supernatant showed no significant effect on these cells. Anticardiolipin antibody, another autoantibody purified from the serum of patients with SLE, also inhibited the proliferation of rat mesangial cells but to a lesser extent. In the presence of antibodies to dsDNA (100 IU/ml), the mesangial cells became spherical and clustered together, which was very different from the original stellate appearance. These autoantibodies also depolarised the membrane potential of mesangial cells. Antibodies to dsDNA decreased the syntheses of prostaglandin E2, 6-keto-prostaglandin F1 alpha and thromboxane B2 by mesangial cells. In an in vivo study, the antibodies to dsDNA showed a strong affinity for the glomeruli when intravenously injected into rats. These results suggest that the nephrotropic antibodies to dsDNA can directly damage the glomerular mesangial cells in addition to the formation of immune complexes with DNA which may cause kidney inflammation and tissue destruction.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Antibodies, Antinuclear; Cell Division; Cells, Cultured; Dinoprostone; Glomerular Mesangium; Humans; Lupus Erythematosus, Systemic; Male; Membrane Potentials; Rats; Rats, Inbred Strains; Thromboxane B2

To determine whether the amount of cyclooxygenase metabolites correlates with the development of lupus nephritis, intrarenal eicosanoid production was measured in autoimmune mice. Disease progression was related to the renal biosynthesis of prostaglandin (PGE2), prostacyclin (6 keto PGF1 alpha), and thromboxane (TXB2) using the MRL-lpr and NZB X NZW F1 hybrid mouse strains with predictably progressive forms of renal disease that mimic the human illness. Mice were evaluated for renal disease by measuring urinary protein excretion and renal immunopathological conditions and these features were related to renal eicosanoid production. These studies show that: (a) intrarenal synthesis of TXB2 increased incrementally in MRL-lpr and NZB X NZW F1 hybrid mice as renal function deteriorated and renal pathologic events progressed; (b) there were no consistent increases in the levels of two other cyclooxygenase metabolites, PGE2 or 6 keto PGF1 alpha; (c) increased TXB2 production occurred in the renal medulla, cortex, and within enriched preparations of cortical glomeruli; (d) when renal disease was prevented by pharmacologic doses of PGE2, intrarenal TXB2 did not increase; (e) administration of a dose of ibuprofen (9 mg/kg), a cyclooxygenase inhibitor capable of reducing 90% of platelet TXB2 without affecting intrarenal levels, did not retard the progression of renal damage. Taken together, these data indicate that the intrarenal level of TXB2 rises in relation to the severity of murine lupus nephritis. Furthermore, because of the potential deleterious effects of TXA2, enhanced production of this eicosanoid may be an important mediator of renal injury.

Topics: Animals; Dinoprostone; Female; Glomerulonephritis; Ibuprofen; Kidney; Kidney Glomerulus; Lupus Erythematosus, Systemic; Male; Mice; Mice, Inbred NZB; Prostaglandins E; Prostaglandins F; Proteinuria; Species Specificity; Thromboxane B2

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.

Topics: Adolescent; Adult; Aged; Blood Platelets; Chronic Disease; Dinoprost; Dinoprostone; Epoprostenol; Female; Gas Chromatography-Mass Spectrometry; Glomerulonephritis; Humans; Ibuprofen; Kidney; Kidney Function Tests; Lupus Erythematosus, Systemic; Middle Aged; Prostaglandins E; Prostaglandins F; Radioimmunoassay; Thromboxane A2; Thromboxane B2

Dietary supplementation of fish oil as the exclusive source of lipid suppresses autoimmune lupus in MRL-lpr mice. This marine oil diet decreases the lymphoid hyperplasia regulated by the lpr gene, prevents an increase in macrophage surface Ia expression, reduces the formation of circulating retroviral gp70 immune complexes, delays the onset of renal disease, and prolongs survival. We show that a fatty acid component uniquely present in fish oil but not in vegetable oil decreases the quantity of dienoic prostaglandin E, thromboxane B, and prostacyclin normally synthesized by multiple tissues, including kidney, lung, and macrophages, and promotes the synthesis of small amounts of trienoic prostaglandin in autoimmune mice. We suggest that this change in endogenous cyclooxygenase metabolite synthesis directly suppresses immunologic and/or inflammatory mediators of murine lupus.

Topics: Animals; Dinoprostone; Fatty Acids, Unsaturated; Female; Fish Oils; Histocompatibility Antigens Class II; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphocyte Activation; Macrophages; Male; Mice; Mice, Mutant Strains; Oils; Prostaglandin-Endoperoxide Synthases; Prostaglandins E; Proteinuria; Safflower Oil; Thromboxane B2

In patients with rheumatoid arthritis high levels of prostaglandin E1 have been found in the joint fluid, and its increased production by adherent synovial cells and macrophages clearly supports the notion that this arachidonic acid metabolite is involved in the pathology of the disease. Besides its known inflammatory qualities and the suppressive effects on various lymphocyte functions prostaglandin E2 has proved to be an essential cofactor in the secretion of the lymphokine osteoclast activating factor. In this study we have discovered an enhanced release of prostaglandin E1 and thromboxane B2 from a subpopulation of blood monocytes from patients with rheumatoid arthritis and active systemic lupus erythematosus. No correlation between prostanoid release from monocytes and inflammatory activity of the disease was found. However, even monocytes from patients with early stage or mild inflammatory activity displayed a 'stimulated' arachidonic acid metabolism. In contrast only patients with active systemic lupus erythematosus showed in this respect comparable secretory activity or monocytes. Our findings may point to a possible pathogenic role of prostanoids in rheumatoid arthritis, which may also have some implication for the early diagnosis of this disease and for its differentiation from other chronic inflammatory rheumatic conditions.

Topics: Arthritis; Arthritis, Rheumatoid; Blood Sedimentation; Female; Humans; Lupus Erythematosus, Systemic; Lymphoproliferative Disorders; Male; Monocytes; Prostaglandins E; Thromboxane B2; Thromboxanes

Topics: Alprostadil; Animals; Antibodies, Antinuclear; Antigen-Antibody Complex; Cyclooxygenase Inhibitors; DNA; Female; Ibuprofen; Kidney Glomerulus; Lupus Erythematosus, Systemic; Mice; Mice, Inbred NZB; Prostaglandin Antagonists; Prostaglandins E; Proteinuria; Thromboxane B2