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 conditioned medium on the biosynthesis and glycosylation profile of acute phase proteins secreted by the human hepatoma cell line Hep G2 was studied. Conditioned medium was prepared from nonactivated [CM-LPS(-)] and ex vivo lipopolysaccharide activated [CM-LPS(+)] monocytes from eight patients with active rheumatoid arthritis (RA), five patients with active systemic lupus erythematosus (SLE), and seven healthy subjects. The biosynthesis of albumin, alpha 1-antichymotrypsin and alpha 1-proteinase inhibitor and the profile of glycosylation of proteinase inhibitor were analysed. CM-LPS(-) from patients with SLE had a similar effect to CM-LPS(-) from healthy subjects. In contrast, CM-LPS(-) from patients with RA had the same effect as CM-LPS(+) from healthy donors. A similar effect to that of CM-LPS(+) of healthy subjects was seen with CM-LPS(+) from patients with SLE and with CM-LPS(+) from patients with RA. The treatment of CM-LPS(+) with antibodies against interleukin 6 neutralised most of its ability to induce changes in the biosynthesis and glycosylation of acute phase proteins. Antibodies to interleukin 1 and tumour necrosis factor alpha had only a limited effect on the ability of CM-LPS(+) to induce changes of albumin and alpha 1-antichymotrypsin syntheses, whereas they had no effect on the biosynthesis and glycosylation of proteinase inhibitor. These results indicate that: (a) monocytes isolated from patients with active SLE and active RA have different capabilities of inducing alterations of acute phase proteins in vitro; (b) ex vivo activation of monocytes from patients with SLE leads to the full induction of its capabilities to change acute phase proteins, whereas the activation of monocytes from patients with RA has no additive effects; and (c) interleukin 6 seems to be a major cytokine involved in the regulation of the glycosylation pattern of acute phase proteins.
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PMID:Different capabilities of monocytes from patients with systemic lupus erythematosus and rheumatoid arthritis to induce glycosylation alterations of acute phase proteins in vitro. 137 63

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

Because of the potential importance of interleukin 1 (IL-1) in modulating inflammation and the observations that human blood neutrophils (PMN) express IL-1 receptors (IL-1R) and synthesize IL-1 alpha and IL-1 beta, we studied the IL-1R on blood PMN from a group of patients with the sepsis syndrome. We report a marked enhancement in the sites per cell of IL-1R expressed on sepsis-PMN of 25 consecutively studied patients compared to 20 controls (patient mean = 9,329 +/- 2,212 SE; control mean = 716 +/- 42 SE, respectively). There was no demonstrable difference in the Kd of IL-1R on sepsis-PMN (approximately 1 nM) as determined by saturation curves of 125I-IL-1 alpha binding and the IL-1R on sepsis-PMN had an apparent Mr approximately 68,000, a value like that of normal PMN. Cytofluorographic analysis indicated that the sepsis-PMN phenotype is a single homogeneous population with respect to IL-1R expression. In contrast, expression of the membrane complement receptor CR3 is not increased on sepsis-PMN. Similar increases in expression of IL-1R were not observed in various other inflammatory processes, including acute disseminated inflammation and organ failure not caused by infection, acute infection without organ failure, and immunopathologies such as active systemic lupus erythematosus and rheumatoid arthritis. Enhanced expression of IL-1R was not related simply to the state of myeloid stimulation. Increased expression of IL-1R on normal PMN was induced in vitro by incubating cells with recombinant human granulocyte-macrophage/colony-stimulating factor for 18 h and this response was inhibited by cycloheximide, suggesting the possibility that de novo synthesis of IL-1R might occur in PMN during the sepsis syndrome.
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PMID:Increased expression of the interleukin 1 receptor on blood neutrophils of humans with the sepsis syndrome. 183 97

The synovial fluid in affected joints of rheumatoid arthritis (RA) patients contains many cells, in numbers strongly correlated with the severity of disease. As the disease worsens and the cell count increases, the polymorphonuclear leucocyte becomes the predominant cell type. Although the inflammatory cytokines interleukin 1 (IL-1) and tumour necrosis factor (TNF) have no direct neutrophil-attractant activity, they are both potent inducers of interleukin 8 (IL-8) in a variety of cell types. Chemotactic attraction of neutrophils is a major activity of IL-8. Examination of a number of synovial fluids showed that significant levels of IL-8 are present in a high proportion of RA cases (10 out of 17), at concentrations directly related to the number of cells in the joint, and to circulating C-reactive protein (CRP) levels. The cytokine is present only at background levels in other diseases accompanied by arthritic manifestations, including systemic lupus erythematosus (SLE) and induced arthritis. The progressive joint destruction seen in all cases where high IL-8 levels were measured, coupled with the neutrophil-rich cell count and the strong correlation between concentration of IL-8 and both serum CRP and cellular influx into the joint, is strongly suggestive of a pathogenic role for IL-8 in RA.
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PMID:Presence of NAP-1/IL-8 in synovial fluids indicates a possible pathogenic role in rheumatoid arthritis. 188 89

We have developed a quantitative assay for IgG autoantibodies against IL-1 alpha using protein A-Sepharose CL-4B. We examined the autoantibodies in sera from 107 healthy subjects, 151 patients with rheumatoid arthritis (RA), 64 patients with systemic lupus erythematosus (SLE) and 16 patients with systemic sclerosis. The frequency of positive sera for the autoantibodies in patients with RA was 16.6%, which was about three times more frequent (P less than 0.01) than that in healthy subjects (5.6%) or that in patients with SLE (4.7%). Only one serum of 16 patients with systemic sclerosis was positive for the autoantibodies. Neutralizing activity of the autoantibodies was demonstrated by murine thymocyte proliferation assay. The concentrations of IgG at 50% inhibition of IL-1 alpha (15 pM) induced thymocyte proliferation ranged between 0.1 and 0.5 mg/ml. A time-course study showed fluctuations of the titres of the autoantibodies in parallel with the disease activity of RA. These results suggest that the anti-IL-1 alpha autoantibodies present in the sera and possibly some other body fluids may be involved in the regulation of IL-1 activity in vivo.
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PMID:Anti-IL-1 alpha autoantibodies in patients with rheumatic diseases and in healthy subjects. 189 21

Elevated spontaneous IgG production is characteristic of SLE. To identify the factors that support it, IL-6, a cytokine with an important role in the differentiation of IgG-secreting cells, was studied in SLE patients. Higher than normal levels of IL-6 were found, by a B9 assay, in sera of 63 of 70 patients (p less than 0.05). IL-6 was detected in 36 of 37 active SLE sera in higher titers (p = 0.009) than those for inactive SLE (n = 33), which were higher (p less than 0.05) than healthy controls (n = 15). IL-6 mRNA was detected in freshly isolated PBMC of 11 of 11 patients but not in normal PBMC, whereas IL-1 mRNA was detected only in patients with active disease. IL-6 activity was recovered from PBMC of four SLE patients, but not from four normal donors. By immunoperoxidase, IL-6 was detected in the cytoplasm of SLE monocytes and lymphocytes. When SLE PBMC were grown in short term cultures with no deliberate stimulation, expression of the IL-6 gene declined rapidly. Accordingly, the spontaneous production of IgG by SLE PBMC could be enhanced by exogenous IL-6. Spontaneous IgG production was diminished by 20 to 65% in the presence of neutralizing antibodies to IL-6, TNF-alpha, or IL-1. In contrast, neutralization of endogenous IL-4 increased production by approximately 40%. Anti-TNF-alpha treatment decreased IL-6 content of PBMC cultures, whereas anti-IL-4 augmented it, and exogenous IL-6 reversed anti-TNF-alpha effects on IgG production. Therefore, it is possible that the neutralization of TNF-alpha and IL-4 affected IgG production by modulating the synthesis/activity of IL-6. These results support the concept that SLE B cell hyperactivity is promoted by dysregulation of endogenous cytokines and suggest that IL-6, in particular, has an important pathogenic role.
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PMID:Elevated levels of endogenous IL-6 in systemic lupus erythematosus. A putative role in pathogenesis. 205 Oct 17

CR1 (CD35) and CR2 (CD21) are structurally related integral transmembrane glycoproteins that function as cellular receptors for human C3b and C3dg, respectively. The primary sequence of the most common structural allotype of CR1 and that of CR2 have been established, and ligand binding on the molecules has been mapped. CR1 and CR2 genes are located in close vicinity in the RCA locus of chromosome 1. CR1 has a wide cellular/tissular distribution and mediates a variety of biologic functions, including the transport of C3-bearing immune complexes on erythrocytes, enhancement of phagocytosis, induction of IL-1 secretion and enhancement of B-cell differentiation. Expression of CR2 is restricted to B lymphocytes and follicular dendritic cells. The receptor modulates B-cell growth. CR2 also serves as the receptor for EBV and determines the cellular tropism of the virus. This review discusses the molecular biology and functional characteristics of CR1 and CR2. It focuses on alterations of expression of the receptors in disease, with particular emphasis on the genetic and acquired factors that contribute to the defective expression of CR1 in patients with systemic lupus erythematosus.
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PMID:Deficiencies of human C3 complement receptors type 1 (CR1, CD35) and type 2 (CR2, CD21). 216 22

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

The mechanism of the spontaneous activation of B cells in patients with SLE was analyzed from the standpoint of the production of IL-1 from B cells and the expression of IL-1R on B cells. SLE B cells spontaneously produced IL-1-like factors which stimulated murine thymocyte proliferative responses. Their m.w. was about 17,000 and their isoelectric point was 4.8. The IL-1-like activity produced by B cells was absorbed with rabbit anti-IL-1 alpha antibody, but not with anti-IL-1 beta antibody. The differentiation of SLE B cells was enhanced by rIL-1 alpha, beta or IL-1-like factors produced by SLE B cells in a concentration-dependent manner. SLE B cells expressed large number of IL-1R detected by FITC-conjugated IL-1 alpha. By a Percoll gradient density centrifugation, IL-1-producing cells and B cells responsive to IL-1 were enriched in a higher density fraction, but were reduced in a lower density fraction. IL-1R-positive B cells were enriched in the lower density fraction, but were depleted in the higher density fraction. However, the expression of IL-1R on the lower density B cells was reduced by 2-day culture. The expression of IL-1R on the higher density B cells was increased during a 2-day culture. Anti-class II antibody inhibited the production of IL-1R on the higher density B cells. These results suggest that the cellular interaction among B precursor cells mediated by class II Ag induces the production of IL-1 and the expression of its receptors on their surface and the interaction between IL-1 and its receptors stimulates B precursor cells to spontaneously differentiate into Ig-producing cells as an autocrine mechanism in patients with SLE.
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PMID:Inhibitory effect of anti-class II antibody on the spontaneous activation of B cells in patients with systemic lupus erythematosus. Analysis with IL-1 production and IL-1 receptor expression. 252 67

TNF and IL-1 are potent immunologic and inflammatory cytokines. We have previously reported increased levels of mRNA for TNF alpha and IL-1 beta in MRL-lpr mice with lupus nephritis. To determine whether the increased levels of TNF and IL-1 mRNA are a more general feature of mice with lupus nephritis we studied cytokine gene expression in female NZB x NZW F1 (NZB/W) mice by Northern blot analysis. Enhanced steady state levels of mRNA for TNF alpha and IL-1 beta, but not IL-1 alpha, were detected in the renal cortices of animals with lupus nephritis. To determine whether administration of TNF or IL-1 would accelerate renal injury and mortality, we injected murine rTNF alpha or rIL-1 alpha i.p. into female NZB/W or C3H/FeJ mice at two doses, 2.0 micrograms or 0.2 micrograms, three times weekly for 2 or 4 mo beginning at 2 or 4 mo of age. Administration of the lower dose of each cytokine accelerated renal disease and mortality rate when treatment was initiated at 4 mo of age. At the higher dose, neither cytokine promoted disease. Treatment administered from 2-4 mo of age did not accelerate renal disease. This observation suggests that in order to cause renal injury, these cytokines must interact with other pathologic features present in these animals after 4 mo of age. These findings support the hypothesis that TNF and IL-1 can contribute to nephritis in murine models of lupus. Taken together with previously published data, we propose that TNF and IL-1 have differential dose effects on renal disease. The dose of TNF and IL-1 and the stage of disease activity dictate the pathogenic action of these cytokines.
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PMID:Tumor necrosis factor and IL-1 in New Zealand Black/White mice. Enhanced gene expression and acceleration of renal injury. 258 2


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