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)

Anti-double-stranded DNA antibodies (anti-DNA) purified from pooled active SLE sera by lambda phage DNA-affinity chromatography was found to affect phytohemagglutinin (PHA) and pokeweek mitogen (PWM)-induced responses of normal mononuclear cells. Anti-DNA at a concentration of 0.25 mg/ml (equivalent to 21 units/ml of DNA binding activity) significantly suppressed the PHA-induced [3H]thymidine incorporation of mononuclear cells in 3 days of culture but had no effect on 5-day and 7-day cultures. In contrast, a biphasic effect of anti-DNA on PWM response was found such that early phase (3-day culture) was inhibited whereas late phase (from 5 days to 9 days of culture) was enhanced by the antibodies. Anti-DNA also increased the immunoglobulin synthesis by PWM-stimulated B cells. The inhibition of PHA response in 3-day culture by anti-DNA is not due to changes in T cell subpopulations. Because interleukin 1 (10 units/ml) could restore the PHA response, it appears that anti-DNA suppressed the IL-1 production by monocyte/macrophage. The biphasic effect of anti-DNA on PWM response is the result of monocyte impairment and B cell stimulation by the antibodies. In the early phase (on day 3) the inhibition would seem to be due to impairment of accessory cell function by anti-DNA, though in late phase (after day 5) the anti-DNA may stimulate B lymphocytes to incorporate more thymidine in the presence of PWM. These biological effects of anti-DNA in vitro resemble the in vivo immunologic disorders in patients with SLE, in that impaired cell-mediated immunity and B cell hyperactivity are frequently observed.
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PMID:Alteration of mitogenic responses of mononuclear cells by anti-ds DNA antibodies resembling immune disorders in patients with systemic lupus erythematosus. 259 47

In order to investigate the mechanism of polyclonal B cell activation in systemic lupus erythematosus (SLE), spontaneous production of interleukin 1 (IL-1) and B cell stimulating factor (BSF) activity by B cells from SLE patients and normal subjects were examined. In both active and inactive SLE, spontaneous IL-1 and BCDF production was significantly increased as compared with normal subjects. However, BCGF activity of B cells from patients with SLE was not significantly increased. After IL-1 activity was absorbed by anti-IL-1 antibody, BCGF and BCDF activities were remained. Low density (larger) B cells separated by Percoll gradient was significantly increased in percentage in SLE patients. However, the population of higher density (smaller) B cells could produce BCGF and BCDF activity in SLE. It is suggested that SLE B cells produce IL-1 and BSF spontaneously and that these factors may play an important role for polyclonal B cell activation in SLE.
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PMID:[Spontaneous production of interleukin-1 and B cell stimulating factors by B cells from patients with systemic lupus erythematosus]. 261 69

Culture supernatants of B cells from patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in the active stage enhanced interleukin 2 (IL-2) dependent proliferation of CTLL A/J cells. This activity, designated B cell-derived growth-enhancing factor-2 (BGEF-2), was recovered by gel filtration of a molecular weight between 15,000 and 20,000. BGEF-2 itself did not show IL-2 activity nor IL-1 activity, and BGEF-2 activity was not detected in the following cytokines: Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), interleukin 4 (IL-4), interleukin 5 (IL-5) and interleukin 6 (IL-6). Furthermore, BGEF-2 was distinguishable from B cell-derived growth-enhancing factor described in a previous paper [Kang et al. (1987) J. Immunol., 139, 1154-1160]. BGEF-2 was produced by B cells from patients with RA or SLE only when the patients were in the active stage. BGEF-2 enhanced IL-2-dependent growth of peripheral blood T cells from patients with active RA, but did not enhance the growth of T cells from healthy volunteers. These results suggest that BGEF-2 is a B cell-derived lymphokine which plays an important role in the pathogenesis of RA and SLE.
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PMID:IL-2 enhancing factor(s) in B cell supernatants from patients with rheumatoid arthritis or systemic lupus erythematosus. 262 61

Antibodies that bind to endothelial cells have been identified in patients with diverse forms of vasculitis and thrombosis. Sera from patients with systemic lupus erythematosus contain both complement-fixing antibodies and immune complexes that bind to cultured endothelial cells. Sera from patients with heparin-associated thrombocytopenia and thrombosis contain antibodies that react with heparin bound to the endothelium and cross-react with heparan sulfate synthesized by endothelial cells. Children with Kawasaki syndrome may develop cytolytic IgM antibodies that recognize surface antigens induced on endothelial cells by interferon-gamma, interleukin 1, and tumor necrosis factor. The presence of alloantibodies to tissue-restricted polymorphic antigens expressed by endothelial cells is frequently associated with thrombotic microvascular injury and hyperacute allograft rejection. Binding of antibodies and immune complexes to endothelial cells in vitro initiates platelet adherence, production of tissue factor, and secretion of plasminogen activator inhibitor. Antibody-mediated endothelial cell injury may play a role in other vascular disorders of unknown cause.
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PMID:Disorders associated with antibodies to endothelial cells. 266 9

Decreased interleukin-2 (IL-2) production by lymphocytes in vitro has previously been demonstrated in patients with systemic lupus erythematosus (SLE). In the present study, we examined whether inhibitory factors in SLE patient sera are involved in defective IL-2 production. Our results indicate that purified IgG fractions of some SLE sera inhibit IL-2 production at 2 distinct phases of the IL-1-dependent IL-2 production system in vitro: first, by binding to adherent cells and probably inhibiting IL-1 production by macrophages, similar to the action of anti-HLA-DR antibodies, and second, by binding to T cells and blocking the interaction of IL-1 and T cells.
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PMID:Two types of antibodies inhibiting interleukin-2 production by normal lymphocytes in patients with systemic lupus erythematosus. 268 69

Serum concentrations of interferon alfa, interleukin 1, and tumour necrosis factor alpha were measured in 25 untreated patients with systemic lupus erythematosus (SLE). A close correlation was found between serum concentrations of interferon alfa and the degree of fever, while no significant correlations were found between fever and interleukin 1 or tumour necrosis factor alpha. These results suggest the possible involvement of interferon alfa in the pathogenesis of fever in SLE.
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PMID:Possible involvement of interferon alfa in the pathogenesis of fever in systemic lupus erythematosus. 281 22

BXSB male mice serve as one of several murine models of human systemic lupus erythematosus. T-cell abnormalities in these mice involve decreased production of and responsiveness interleukin 2 (IL-2) and are age-related. The studies presented here investigated the mechanism of these T-cell defects. The results suggest that excessive suppressor-T-cell activity as well as soluble inhibitors of IL-2 production and activity, including PGE, are not responsible for the low levels of IL-2 observed in culture supernatants of Con A-stimulated lymphocytes from "old" (3-6 months) BXSB male mice. Supplementation of Con A-stimulated lymphocyte cultures from BXSB male mice with human IL-1 or normal murine accessory cells did not augment IL-2 production. Reduced proliferative responses were observed in bulk cultures of Con A- or alloantigen-stimulated "old" BXSB male lymphocytes, which were not enhanced by exogenous IL-2. Limiting dilution analysis revealed reduced frequencies of Con A- and alloantigen-inducible IL-2-reactive T cells in these mice. These results suggest intrinsic defects in the ability of T cells from "old" BXSB male mice to be activated to produce and respond to IL-2.
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PMID:Production of and responsiveness to interleukin 2 in autoimmune BXSB mice. 295 44

We studied the effects of cyclosporin A (CYA) on the production of various lymphokines and on the suppressor functions of peripheral blood mononuclear cells (MNC) of ten untreated SLE patients. CYA was found to inhibit the production of IL-2 and of B cell stimulating factor (BSF) by both normal and SLE MNC but it did not alter the LPS-driven production of IL-1 by either of them. However, it did abrogate the spontaneous release of IL-1 by SLE monocytes. CYA strongly inhibited the production of IL-3-like activity by normal T cells, an effect noticed only on cells from 4 SLE patients, three of whom were in remission. Addition of CYA significantly increased suppressor cell function by cells from all SLE patients. T cell clones could be obtained from two of them by using CYA-conditioned medium containing IL-3. These clones were found to have strong suppressor capacity.
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PMID:Presence of an IL-3-producing suppressor T cell resistant to cyclosporin A in the peripheral blood of patients with systemic lupus erythematosus. 297 65

The influence of interleukin 1 (IL-1) on IgG synthesis was studied in patients with systemic lupus erythematosus (SLE). Spontaneous IgG synthesis was assessed by culturing peripheral blood mononuclear cells in media for 7 days. The effect of adherent cell supernatants (ACS) on spontaneous IgG synthesis was also assessed, based upon previous studies showing that ACS contributes significantly more to IgG synthesis in SLE than it does in normals. Antiserum against IL-1 reduced spontaneous IgG synthesis by approximately 90% in SLE and normal mononuclear cell cultures. The antiserum caused a parallel reduction in the number of Ig-secreting B cells. Adsorption of SLE ACS with Sepharose-bound antiserum against IL-1 prevented ACS-induced increases in IgG synthesis. Affinity-purified or recombinant IL-1 added to media did not significantly stimulate IgG synthesis. Incubation of ACS with a monoclonal antibody against interferon-gamma had no effect on IgG synthesis, and no detectable interferon activity was found in ACS using a virus inhibition assay. Stimulation of IgG production by autologous mononuclear cell supernatants correlated directly with the presence of clinically active disease, suggesting that these in vitro observations may be important to the disease process. These findings demonstrate that hyperactive B cells from patients with SLE are regulated by factors released by adherent mononuclear cells, probably monocytes. The presence of IL-1 is crucial, but may not be sufficient, for spontaneous and ACS-induced IgG synthesis. Inhibiting or blocking the production of IL-1 may provide a means of reducing abnormal immunoglobulin synthesis in SLE.
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PMID:The effect of interleukin 1 on IgG synthesis in systemic lupus erythematosus. 311 64

In conclusion, IL-1 has multiple biologic activities relevant to rheumatic diseases. It mediates the acute-phase response, and exerts control over many metabolic functions of connective tissue, including muscle, bone, cartilage, synovium, and endothelium. IL-1 also has a profound effect on leukocyte function. Although few clinical studies have been reported, there is suggestive evidence that IL-1 plays a role in the pathogenesis of arthritis, scleroderma, SLE and vasculitis. That drugs useful in the therapeutic management of these conditions influence IL-1 activity provides indirect support for the involvement of IL-1 in pathogenesis. Clearly, further studies are needed in this area. With the recent development of recombinant preparations of IL-1, further investigation of IL-1 in connective tissue metabolism and clinical rheumatic disease can be carried out. Finally, the future development of pharmacologic agents specifically designed to alter IL-1 responses may allow specifically targeted therapy for rheumatic diseases.
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PMID:Biologic activities of interleukin-1 relevant to rheumatic diseases. 312 83


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