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)

Patients with systemic lupus erythematosus experience clinical exacerbation during superimposed bacterial infection. Previous studies in mice indicated that heightened immune phenomena during exposure to bacterial lipopolysaccharide (LPS) appear to be related, in part, to polyclonal B cell activation, to abnormal disposal of immune complexes (IC), and to increased localization of IC in tissues. To investigate whether such effects were reversible, we administered bacterial LPS to C57BL/6 mice for 5 weeks. Control mice received vehicle alone. We then discontinued LPS, and 6 weeks later LPS and control mice were challenged with a subsaturating dose of radiolabeled IC; the removal of IC from the circulation, their localization in the liver, spleen, and kidney were determined. In comparison to values in control mice, in mice previously exposed to LPS, serologic features of polyclonal B cell activation persisted; liver uptake of pathogenic IC (greater than Ag2Ab2) was normal, but removal of small size IC (less than or equal to Ag2Ab2) from the circulation was delayed; localization of IC in the kidneys was enhanced, and pathologic proteinuria developed. The effects of repeated exposure to bacterial LPS are partially reversible, but they last long after LPS is discontinued and may contribute to altered disposal of IC, enhanced organ localization of IC, and organ dysfunction.
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PMID:Defective disposal of immune complexes and polyclonal B cell activation persist long after exposure to bacterial lipopolysaccharide in mice. 281 Dec 99

Lumin was administered at doses of 0.1 to 100 micrograms/kg for 5 months to NZB/W F1 mice as the model animal for studying systemic lupus erythematosus (SLE), a human autoimmune disease. The increase in anti-thymic autoantibody level was significantly inhibited at doses of 1 to 100 micrograms/kg. Also, the induction of suppressor T cells by concanavalin A was significantly promoted. In addition, recovery activity was significantly observed, over-coming the reduction in plaque-forming cell (PFC) response of anti-sheep erythrocytes at a dose of 100 micrograms/kg, as well as the reduction in PFC response of anti-trinitrophenylated-lipopolysaccharide at doses of 0.1 to 100 micrograms/kg. The above results prove that lumin exhibits an immunomodulating effect against immune disease in mice.
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PMID:[Immunopharmacological actions of lumin (II): Effect of lumin administration in NZB X NZW (B/W) F1 mice]. 295 70

The in vivo effects of a variety of inflammatory stimuli on complement C4 and factor B plasma levels have been examined. MRL/++ (H-2k) mice were given intraperitoneal injections of lipopolysaccharide, turpentine, Corynebacterium parvum pyridine extract residue or high doses of indomethacin. All of these treatments induced an increase in plasma factor B concentrations, which in the case of C. parvum was dose dependent and persisted for at least 7 days. Lipopolysaccharide, turpentine and indomethacin produced decreases in plasma complement C4. C. parvum, however, produced an increase in plasma complement C4 to approximately 240% of controls which was independent of gender. It was also independent of major histocompatibility complex haplotype, since the same effect was seen in C57B1/6J-bg/bg and C57B1/6J-bg/+ mice. The gross increment in complement C4 was, however, related to the major histocompatibility complex. H-2K mice ("low complement C4") had smaller increments than H-2b ("high complement C4"). Mycobacterium bovis (BCG) also produced a transient increase in C4 in the H-2b mice as well as a prolonged increase in factor B levels. These data (i) suggest that different inflammatory stimuli induce different mediators which may have differential effects on factor B and complement C4 synthesis, and (ii) emphasize the independent regulation of complement C4 and factor B. Qualitative variations in the mediators elaborated during chronic inflammatory diseases may help determine complement C4 fluctuations in systemic lupus erythematosus and the wide range of complement C4 concentrations seen in MRL/1 pr mice with active immune complex disease.
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PMID:Differential effect of inflammatory stimuli on murine plasma C4 and factor B concentrations. 305 73

T cells from murine lupus strains manifest complex defects in interleukin 2 (IL 2) production and receptor expression. The capacity of B cells from such mice to utilize IL 2 as a growth factor has not been previously reported and is examined herein. Anti-Thy-1.2 plus complement-treated spleen cells from 6-8-week-old autoimmune MRL-lpr/lpr mice and from age and sex-matched immunologically normal CBA/J mice were cultured with lipopolysaccharide (LPS) for 36 h and analyzed for the expression of IL 2 receptors using the monoclonal antibody 7D4. The percentage of B cells expressing IL 2 receptors was comparable in MRL-lpr/lpr and CBA/J mice. In contrast to those from CBA/J, BALB/c and (BALB/c X NZW)F1 mice, LPS-stimulated B cells from MRL-lpr/lpr and from (NZB X NZW)F1 mice were capable of proliferating in response to IL 2. Fractionation of MRL-lpr/lpr B cells using Percoll gradient density separation demonstrated that the IL 2-responsive population consisted predominantly of large cells. In addition, unfractionated B cells from MRL-lpr/lpr mice were found to be substantially more responsive to IL 2 than those from CBA/J and BALB/c mice following activation with anti-immunoglobulin plus LPS. The hyper-responsiveness to IL 2 may be a consequence of the state of activation of autoimmune B cells and is of potential importance in the pathogenesis of systemic lupus erythematosus.
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PMID:Interleukin 2 is a proliferative signal for B cells from autoimmune mice. 309 46

Activation/proliferation of mouse and human T and B cells is associated with expression and subsequent release of interleukin 2 receptors (IL 2R) into the milieu. The soluble form of IL 2R, at least in part, retains its ability to bind to IL 2 and to anti-receptor antibodies, but its exact structure remains unknown. Because systemic lupus erythematosus (SLE) is associated with T and B cell activation, we have used monoclonal anti-IL 2R antibodies in an ELISA to measure levels of IL 2R in sera of various lupus strains. High levels of the released receptor were found at an active clinical stage in sera of four autoimmune strains of mice homozygous for the lpr (lymphoproliferation) gene that causes T cell expansion, massive lymphoid organ enlargement, and promotes the autoimmune process. High levels were also found in lupus mice characterized primarily by B cell proliferation (BXSB males) and in (NZB X W)F1 mice characterized by T and B cell activation. Similarly high IL 2R serum levels could be induced experimentally in normal mice injected with immunostimulants such as bacterial lipopolysaccharide or Freund's complete adjuvant. The results indicate that IL 2R serum levels may provide a good marker of ongoing lymphoid cell activation/proliferation, and thus might be useful in the follow-up of patients with systemic autoimmune or other lymphoproliferative disorders. The biologic roles, if any, of the soluble form of IL 2R and its effects in normal and abnormal conditions remain to be determined.
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PMID:Elevated titers of cell-free interleukin 2 receptor in serum of lupus mice. 311 68

Anticardiolipin antibodies (ACA) were detected by solid-phase enzyme immunoassay in the majority of sera from patients with Gram-positive and Gram-negative bacterial infections. The response involved all the major immunoglobulin classes IgG, IgM, and IgA. The specificity of the ACA was studied in competitive inhibition experiments with three putative antigens: cardiolipin, lipopolysaccharide (LPS) isolated from Salmonella minnesota, strain Re 595, and synthetic Escherichia coli lipid A. The binding of IgG class ACA from the sera of five patients with Gram-negative infections was effectively inhibited by LPS, whereas 100-fold more cardiolipin was required for comparable inhibition. Pure lipid A was a less effective inhibitor of anticardiolipin activity than LPS. This pattern of reactivity was not seen in sera from patients with Gram-positive infections, syphilis, or systemic lupus erythematosus. Our findings suggest that cardiolipin may not be the inducing antigen for the cardiolipin-binding antibodies that develop in Gram-negative infections.
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PMID:Effective inhibition of cardiolipin-binding antibodies in gram-negative infections by bacterial lipopolysaccharide. 321 87

An assessment of the prophylactic and ameliorative effects of deoxyspergualin (NKT-01), an immunosuppressive agent, was carried out in male MRL/MpJ-lpr/lpr (MRL/1) mice which spontaneously develop lupus-like lesions. When NKT-01 was administered ip daily from the age of either 8 or 19 weeks, diseases such as massive lymphadenopathy, circulating anti-DNA antibody and lupus nephritis were markedly suppressed. The primary response to lipopolysaccharide was significantly reduced in MRL/1 mice administered NKT-01 but the response to sheep red blood cells was not affected. The ability of spleen cells to release interleukins 2 and 3 with or without mitogen was significantly enhanced in mice receiving NKT-01. These findings demonstrate that NKT-01 has therapeutic activity against the development of spontaneous disease in MRL/1 mice.
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PMID:Biological activities of deoxyspergualin in autoimmune disease mice. 326 48

Production of interleukin-1 (IL-1) by glass-adherent monocytes from 18 patients with systemic lupus erythematosus (SLE) was measured. Patients were divided into three groups according to disease activity. A deficient production of IL-1 was found in monocytes of SLE patients both without stimulation and after stimulation with 5 micrograms of lipopolysaccharide. The decreased production correlated with the degree of disease. Addition of phorbol myristate acetate to monocytes caused only partial normalization of the decreased IL-1 production. The IL-1 deficiency in SLE is postulated to be a part of complex abnormalities of cell-mediated immunity in this disease.
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PMID:Interleukin-1-production by monocytes from patients with systemic lupus erythematosus. 350 83

Although ultraviolet (UV) light is generally harmful to patients with systemic lupus erythematosus, most clinical and immunologic studies of UV exposure have evaluated the effects of UV-B (280-320 nm). The long-wavelength UV-A band (320-400 nm), however, is less toxic than UV-B and has different immunologic actions. Therefore, we studied the effect of UV-A irradiation on survival and immunologic function in the (New Zealand black x New Zealand white)F1 hybrid mouse model of systemic lupus erythematosus. Twenty-one (New Zealand black x New Zealand white)F1 mice were treated with 3.5 joules/cm2/day of UV-A light for 5 days each week, beginning at age 10 weeks. A control group consisted of 20 untreated animals. All UV-A-irradiated mice survived to 32 weeks, compared with 12 of 20 mice in the nonirradiated group (P = 0.0013). Splenomegaly was significantly decreased in the irradiated mice (P less than 0.03). Mice that received UV-A treatment combined with depilation had significantly improved lymphocyte responses to phytohemagglutinin and lipopolysaccharide and significantly decreased levels of anti-DNA antibodies compared with mice that received neither treatment. Reductions in spleen size and anti-DNA antibody titer were significantly correlated with improved parameters of lymphocyte function. These results suggest that a relatively small dose of UV-A exerts significant therapeutic action in murine lupus, perhaps through an effect on immunologic regulation.
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PMID:Ultraviolet-A light prolongs survival and improves immune function in (New Zealand black x New Zealand white)F1 hybrid mice. 359 37

Anti-histone antibodies (AHA) are spontaneously produced in NZB/NZW mice as part of their autoimmune disease. IgM AHA are usually not detected until after 4 mo of age, and older female mice switch to the production of IgG AHA. We studied the in vitro production of AHA by spleen cells from young (less than or equal to 12-wk-old) NZB/NZW mice. Despite the absence of elevated serum AHA activity, spleen cells from these mice demonstrated marked spontaneous autoantibody production in culture. In kinetic studies, little in vitro production was detectable after 1 day of culture, and maximal accumulation occurred on day 5. Elevated AHA production was apparent by cells from 2-wk-old NZB/NZW mice, and an age-dependent increase in autoantibody production was also noted. Only AHA of the IgM class were detected in cultures of young spleen cells. The in vitro production of IgM AHA in culture was T cell dependent, depletion of T cells resulting in a 70 to 90% reduction in production, which was corrected by the readdition of T cells. In cultures where both IgM AHA and total IgM secretion were measured, a much greater T cell dependence for AHA production was apparent. The requirement for T cells could also be partially replaced by factors present in concanavalin A supernatant. AHA secretion was induced by lipopolysaccharide by using cells from both NZB/NZW and non-autoimmune mice. Although production was greater with NZB/NZW cells, the difference was much less than that for spontaneous production. Thus, AHA-secreting cells that are dependent on in vitro T cell help are present in young NZB/NZW mice. These studies may help define the mechanisms responsible for selective autoantibody secretion in lupus-like disease.
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PMID:In vitro production of anti-histone antibodies by spleen cells from young autoantibody negative NZB/NZW mice. 387 28


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