Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eicosanoids, lymphokines, and free radicals are known to participate in the pathogenesis of inflammation. Tumour necrosis factor (TNF), interleukin-1 and 6 (IL-1 and IL-6) and colony stimulating factor -1 (CSF-1) are secreted mainly by activated macrophages, whereas T-cells secrete IL-2, IL-3, IL-4 and interferon-gamma (IFN-gamma). In addition, activated macrophages and lymphocytes can also produce eicosanoids and free radicals which have potent pro-inflammatory actions. Eicosanoids, lymphokines, and free radicals can modulate the immune response, cell proliferation, stimulate collagenase and proteases secretion and induce bone resorption; events which are known to be associated with various collagen vascular diseases. On the other hand transforming growth factor-beta (TGF-beta) produced by synovial tissue, platelets and lymphocytes can inhibit collagenase production, suppress T-cell and NK-cell proliferation and activation and block free radical generation and seems to be of benefit in rheumatoid arthritis. Drugs such as cyclosporine, 1,25,dihydroxycholecalciferol and pentoxyfylline can block lymphokine and TNF production and thus, may inhibit the inflammatory process. Essential fatty acids, the precursors of eicosanoids, are suppressors of T-cell proliferation, IL-1, IL-2 and TNF production and have been shown to be of benefit in rheumatoid arthritis, systemic lupus erythematosus and glomerulonephritis. Thus, the interactions between essential fatty acids, eicosanoids, lymphokines, TGF-beta and free radicals suggest that new therapeutic strategies can be devised to modify the course of collagen vascular diseases.
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PMID:Interaction(s) between essential fatty acids, eicosanoids, cytokines, growth factors and free radicals: relevance to new therapeutic strategies in rheumatoid arthritis and other collagen vascular diseases. 172 26

The role of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) in the pathogenesis of the collagen vascular diseases was studied. The serum level of IL-4 was decreased in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD), and was variable in patients with rheumatoid arthritis (RA). The serum level of IFN-gamma was increased in patients with SLE, MCTD and RA. In patients with SLE, there was an inverse correlation between the levels of IL-4 and IFN-gamma. The proliferation and immunoglobulin production of the high-density-B cells in response to IL-4 was suppressed in normal controls, although the degree of suppression was less in patients with SLE. Cell cycle analysis using ethidium bromide demonstrated the similar findings. These data suggest that IL-4 and IFN-gamma might participate in regulating both of growth and differentiation of B cells in vivo. However, immunoglobulin production by whole B cells in response to IL-2 or PHA-induced T-cell factor was extensively facilitated by IFN-gamma in patients with SLE. It is possible that IFN-gamma enhances the differentiation of already-activated B cells, and that polyclonal B cell activation is promoted. Therefore, the failure of the regulatory mechanism by these cytokines might be related to the pathogenesis of these diseases.
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PMID:[Relationship between serum interleukin-4 or interferon-gamma level and B cell abnormality in patients with collagen vascular diseases]. 176 43

The study of T cells in individuals with systemic lupus erythematosus has been limited because a specific marker for the disease has not been identified. To approach this issue, we isolated autoreactive T cell clones from lupus-prone MRL mice, a strain that develops an accelerated form of lupus. These CD4+ T cell clones grew spontaneously from unimmunized mice, and were maintained in culture by intermittent stimulation with syngeneic antigen presenting cells in the absence of exogenous antigen. One autoreactive T cell clone, termed ARTC-1, previously reported to have atypical MHC requirements for activation (both I-Ak and I-Ek were required) and to stimulate B cell proliferation and Ig production in vitro, was found to have an unrestricted pattern of lymphokine secretion. Following stimulation, it produced IL-4, IFN-gamma and IL-2. ARTC-1 induced B cell proliferation both by cell contact and through secretion of soluble lymphokines. B cell proliferation by cell-cell contact was MHC restricted in a manner analogous to ARTC-1 activation by APCs; the B cell response was inhibited by both anti-I-Ak and anti-I-Ek antibodies. The ARTC-1 B cell interaction was also found to result in the production of IgG autoantibodies. These observations suggest that cells such as ARTC-1, if unregulated, could lead to B cell stimulation and autoantibody production in vivo, in the absence of exogenous stimulation. Furthermore, IFN-gamma production by ARTC-1 could also result in enhanced class II expression, leading both to additional T-B cell interactions and to T cell interactions with endogenous cells capable of expressing class II antigens in other organs.
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PMID:Autoreactive T cells from MRL-lpr/lpr mice secrete multiple lymphokines and induce the production of IgG anti-DNA antibodies. 177 9

The ability of T cells to secrete IL-2 in patients with systemic lupus erythematosus (SLE) was investigated. In patients with SLE, impaired IL-2 production by peripheral blood lymphocytes stimulated with mitogens is well known. In this paper, we report that purified T cells stimulated with mitogens, in the presence of Epstein-Barr virus transformed B cells (B-LCL) as an accessory cell, however, could secrete a large quantity of IL-2 as much as normal T cells. In order to study this potential capacity of T cells to secrete IL-2 in patients with SLE, IL-2 secreting T cells were examined. To obtain these cells, T cells were divided into cluster forming cells and noncluster forming cells after short culture of T cells with accessory cells in the presence of Con A. Then the ability of IL-2 production in two kinds of separated T cells was examined. We found that 1) after short culture with B-LCL, the cluster forming T cells could secrete IL-2 when cultured again, but non-cluster forming T cells could not, even in the presence of B-LCL, 2) after short culture with macrophages, in normal donors and SLE patients, noncluster forming T cells were able to secrete a greater amount of IL-2 than cluster forming and undivided T cells when cultured with B-LCL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional T cell subpopulations responsible for hyposecretion of IL-2 in patients with systemic lupus erythematosus. 180 93

Using various monoclonal antibodies to T cell activation molecules it has been shown that purified T cells from patients with active systemic lupus erythematosus overexpress the 4F2, IL-2R (CD25), HLA-DR and T10 antigens. T cells from patients with inactive disease had increased expression of VLA-1 and HLA-DR. Increased T10 expression on T cells from patients with active disease correlated inversely with the production of IL-2, whereas expression of CD25 was slightly increased after 3-day culture with either PHA or anti-CD3. These results provide further evidence of the in vivo activation of T cells in SLE and suggest that such activation comes slowly to a halt upon disease remission.
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PMID:Activation markers on peripheral blood T cells from patients with active or inactive systemic lupus erythematosus. Correlation with proliferative responses and production of IL-2. 181 97

Interferon-gamma activates both in vitro and in vivo macrophage functions. Injection of rat recombinant interferon-gamma (rR-IFN-gamma) induced the expression of interleukin-2 receptors (IL-2R) by peritoneal macrophages from normal BALB/c and MRL-+/+ mice. Moreover, rR-IFN-gamma stimulated in a dose-dependent manner the oxidative burst of cells as revealed by luminol-dependent chemiluminescene (LDCL). Resident peritoneal macrophages from MRL-lpr/lpr (mice that develop a systemic lupus-like syndrome) showed a higher PMA-triggered LDCL response. This enhanced activity was accompanied by an increase in IL-2R expression (30% vs. less than 1%). The "activated" macrophages from rR-IFN-gamma-treated normal mice as well as MRL-lpr/lpr mice did not respond to the addition of recombinant interleukin-2 (rHu-IL-2) by an increase in LDCL. However, rHu-IL-2 triggering became efficient when cells enriched in IL-2R-bearing macrophages were preincubated overnight with rHu-IL-2R. This response may point out a functional role for IL-2R and provide a role for IL-2 in certain macrophage functions.
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PMID:Role of interferon-gamma on the in vivo expression of functional interleukin-2 receptors by murine macrophages. 193 95

In our study, we have measured in vitro proliferation and IL-2 production by human PBL to characterize the interactions between Th cells and accessory cells (AC) involved in responses to either conventional Ag or alloantigens. IL-2 production and proliferative responses to conventional Ag, such as influenza or tetanus, are exclusively dependent on the presence of CD4+ T cells and AC. In contrast, IL-2 and proliferative responses to alloantigen can be mediated by either CD4+ or CD8+ T cells. CD4+ T cells respond to alloantigen using either autologous AC (self-restricted), or allogeneic AC (allo-restricted), whereas CD8+ T cells respond to alloantigen using allogeneic AC only. The understanding of Th cell-AC interactions involved in in vitro allogeneic responses will be important for delineating the Th cell-AC interactions involved in transplantation immunity as well as in clinical disorders characterized by T cell dysfunction such as human immunodeficiency virus infection and systemic lupus erythematosus.
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PMID:Human in vitro allogeneic responses. Demonstration of three pathways of T helper cell activation. 196 49

The authors reported IL-2 production and T cell subpopulation of peripheral blood lymphocytes from patients with systemic lupus erythematosus(SLE). The results indicated that patients with SLE showed a decreased IL-2 production and a decreased T4/T8 cell ratio. The relation between IL-2 production and T4/T8 ratio was also observed. Our data suggest that IL-2 production correlates significantly with T4/T8 cell ratio.
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PMID:[The relationship between IL-2 production and T cell subpopulation in patients with systemic lupus erythematosus]. 198 55

A low-frequency suppressor-cell population in normal peripheral blood inhibits the B-cell CESS response to IL-6, following pokeweed mitogen stimulation. The suppression of IL-6 responsiveness is (i) radiation sensitive, (ii) directed against CESS targets and not mediated by inhibition of IL-6 production, and (iii) associated with nonspecific cytotoxic activity against CESS targets. The generation of these cytolytic cells is also radiation sensitive. A correlation was found between PWM-induced cytotoxicity against CESS and the suppression of IL-6-dependent IgG production. But cytotoxicity toward CESS targets is not responsible for this suppression because (i) IL-2 induces equivalent or greater nonspecific cytotoxicity against CESS in the total absence of suppression of CESS-derived IgG production and (ii) suppression is also induced by mitogen-activated PBL separated from CESS targets by a cell-impermeable membrane. This suppression was not mediated by TNF alpha/beta or IFN-gamma. In systemic lupus erythematosus, suppression of IL-6-dependent IgG production is impaired in patients with active disease (29.2 +/- 13.7%) compared to patients with inactive disease (70 +/- 19.5%) or normal controls (82.8 +/- 9.2%). There is also a defect in mitogen-induced nonspecific cytotoxicity in active SLE (specific lysis 15.1 +/- 3.5%, compared to 34 +/- 4% in normals). Pokeweed mitogen-activated PBL can therefore normally induce suppression of B-cell IL-6 responses and this response is deficient in lupus.
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PMID:Normal mitogen-induced suppression of the interleukin-6 (IL-6) response and its deficiency in systemic lupus erythematosus. 210 95

Recently, IL-1 inhibitors from urine, monocytes, or monocyte lines have been described. The relationship of these inhibitors to the production, release, and immunological effects of IL-1 is unclear. The present studies were initiated to describe and quantitate the production of IL-1 and a 23 to 45-kDa IL-1 inhibitor from human monocytes in response to certain stimuli using a mouse thymocyte system responsive to IL-1. Zymosan stimulated monocytes to produce IL-1 but not IL-1 inhibitor. Adherent immune complexes, human IgG1-4, and Fc fragments, but not F(ab')2, stimulated monocyte production of IL-1 inhibitor and little if any IL-1. Fibronectin and three of its fragments had neither effect. These observations suggest that monocytes produce IL-1 or IL-1 inhibitor in response to two different signals, through "endotoxin or beta-glucan" and Fc receptors, respectively. The inhibitor decreases IL-1-induced CD-1, C3H/HeJ, and D10 G4.1 cells but not IL-2-induced CD-1, C3H/HeJ, or CTLL-2 proliferation. The inhibitor competitively blocked binding of radiolabeled rIL-1 to the IL-1 receptor on murine thymoma cells. Preincubation of thymocytes with the inhibitor prevented IL-1-induced proliferation; however, this effect was reversed by washing thymocytes and inhibitor activity was markedly reduced when added 24 hr after stimulation with IL-1. These observations suggest that the inhibitor acts on IL-1 receptors to prevent thymocyte proliferation. Monocytes from patients with systemic lupus erythematosus produced less IL-1 inhibitor than cells from normal volunteers. The decrease in IL-1 inhibitor production may play a role in disease states.
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PMID:Human monocytes produce IL-1 and an inhibitor of IL-1 in response to two different signals. 239 35


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