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)

To gain a better understanding of inherent gender-related effects on autoimmunity, cytokine genes were examined in female and male New Zealand Black X New Zealand White (B/W) mice, which are a murine model of systemic lupus erythematosus (SLE). In preliminary studies, semiquantitative reverse transcriptase-polymerase chain reaction analysis showed a trend for B/W spleen cell interferon gamma (IFN-gamma) mRNA in B/W female spleen cells to exceed that of males. This difference was obliterated following concanavalin A (Con A) stimulation. Spleen cells from B/W mice of both sexes were then examined at 6, 18, and 27 weeks of age, and results were compared with matched groups of nonautoimmune DBA/2 mice. Pooled splenocytes from all 12 groups of animals were compared simultaneously for expression of mRNA specific for IFN-gamma, interleukin 4 (IL-4) and interleukin 6 (IL-6). Strain was a potent influence on cytokine transcripts. In unstimulated splenocytes from female and male B/W mice, there was a notable trend for IFN-gamma and IL-6 mRNA expression to exceed transcripts from nonautoimmune DBA/2 mice. When comparisons were carried out by gender, a highly significant increase of IFN-gamma transcripts was apparent in B/W females compared to B/W males at the age of 27 weeks. Following Con A incubation, strain and gender differences were eliminated. IL-4 transcript expression was similar in all pools of cells, and age was not an important factor in expression of any transcript. This study represents the first examination of multiple cytokine transcripts in lymphoid cells from B/W mice. In this hormone-sensitive model of SLE, strain and gender determined in vivo expression of IFN-gamma and IL-6 mRNA.
 ...
PMID:Cytokine mRNA expression in the B/W mouse model of systemic lupus erythematosus--analyses of strain, gender, and age effects. 928 84

A 30 year-old female laboratory technician under immunosuppressive treatment because of systemic lupus erythematosus (SLE) developed cutaneous leishmaniasis 8 months after accidental percutaneous inoculation of amastigote culture forms of Leishmania mexicana. Leishmania-specific PCR and restriction analysis patterns were identical for both the laboratory strain and the clinical specimen. The lesion was resistant to local paromomycin and oral ketoconazole, but responded to local application of meglumine antimonate. No signs of dissemination or visceralization occurred during the 5-month period of observation. However, a future recurrence cannot be excluded since a persistent infection even after clinical cure has always to be considered in leishmaniasis. Patients under immunosuppressive therapy are possibly at risk of clinical relapse or disseminating infection although there is no experience with regard to leishmaniasis mexicana. Serious infection may require interferon gamma as part of the treatment which may contribute to deterioration of concomitant diseases like SLE. In any case, the exposure of immunodeficient laboratory workers to Leishmania spp. should be avoided.
 ...
PMID:Accidental Leishmania mexicana infection in an immunosuppressed laboratory technician. 943 71

Interleukin 12 (IL-12) plays a crucial role in defensive immune responses, modulation of cytokine production and is involved in the pathogenesis of some autoimmune diseases. The authors investigated whether decreased in vitro production of IL-12 occurs in systemic lupus erythematosus (SLE), in which the cytokine secreting pattern is predominantly type 2. IL-12 production by SLE peripheral blood mononuclear cells (PBMC) was significantly impaired compared with normal PBMC, and this was not due to decreased numbers of monocytes. After depletion of non-adherent cells from PBMC, monocytes of SLE patients produced significantly less IL-12 than those of controls, but IL-12 levels in SLE and control non-adherent cells supernatants were not significantly different. Exogenous recombinant (r)IL-10 strongly inhibited IL-12 production by both SLE and normal PBMC and anti-IL-10 neutralizing antibody significantly reversed the IL-12 deficiency of SLE PBMC and SLE monocytes, while not affecting normal PBMC. Recombinant interferon gamma (rIFN-gamma) considerably enhanced IL-12 production in both SLE and normal PBMC, but it did not significantly reverse the inhibitory effect of rIL-10 on IL-12 production. IL-12 production was significantly lower in patients with active SLE than those in remission. These results suggest that SLE monocytes may be deficient in IL-12 production and that this is secondary to abnormal production of various cytokines, especially excessive production of IL-10.
 ...
PMID:Impaired production of IL-12 in systemic lupus erythematosus. I. Excessive production of IL-10 suppresses production of IL-12 by monocytes. 951 4

Interleukin 12 (IL-12) is a key cytokine in regulating type 1 or type 2 cytokine production and in determining the nature of immune responses. Our previous studies demonstrated that its production was significantly impaired in systemic lupus erythematosus (SLE) patients and this deficient IL-12 production was mainly mediated by excessive endogenous IL-10. The present study was designed to further reveal the relationships of in vitro IL-12 production with abnormalities of in vivo cytokine synthesis and disease activity in SLE. Experimental results showed that IL-12 production in vitro was inversely correlated with serum IL-10 level, anti-ds DNA antibody level and SLE disease activity index (DAI), but positively correlated with serum interferon gamma (IFN-gamma) level, with which serum IL-10 correlated negatively. Data also showed that serum IL-10 was significantly higher than that of controls and closely correlated with anti-ds DNA antibody level and SLEDAI. The study confirms that deficient IL-12 production in SLE patients is associated with in vivo abnormalities of cytokine production, especially with increased IL-10 production.
 ...
PMID:Impaired production of IL-12 in system lupus erythematosus. II: IL-12 production in vitro is correlated negatively with serum IL-10, positively with serum IFN-gamma and negatively with disease activity in SLE. 951 5

We investigated serum level of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) using an enzyme-linked immunosorbent assay (ELISA) in 59 patients with systemic lupus erythematosus (SLE) and 16 healthy controls. We examined a possible association between serum levels of these cytokines and SLE activity, as well as correlation between IFN-gamma concentration and the level of TNF-alpha and IL-6 and also IL-6 and TNF-alpha. TNF-alpha and IL-6 were detectable in all 59 patients and normal individuals and their level was significantly higher in SLE patients than in the control group (p < 0.001 and p < 0.02, respectively). In contrast IFN-gamma was detectable in 23 (39%) patients and in only 3 (20%) healthy individuals. We found positive correlation between serum concentration of TNF-alpha and IL-6 with SLE activity and no such correlation with IFN-gamma. We also observed positive correlation between serum levels of IFN-gamma and TNF-alpha, IFN-gamma and IL-6 as well as TNF-alpha and IL-6. In conclusion, an increase in the serum levels of TNF-alpha and IL-6 may be useful markers for SLE activity.
 ...
PMID:Association of interferon gamma, tumor necrosis factor alpha and interleukin 6 serum levels with systemic lupus erythematosus activity. 988 17

Interleukin 12 (IL-12) is a heterodimer comprising p35 and p40 subunits which are encoded and regulated separately. The authors previously demonstrated deficient IL-12 production in SLE which correlates negatively with disease activity. The present study was designed to determine whether deficiency of IL-12 and excess production of IL-10 and IL-6 in systemic lupus erythematosus (SLE) are due to aberrant regulation at the gene level. Using semiquantitative RT-PCR assay, it was shown that constitutive expression of IL-12 p35 gene is somewhat impaired in SLE compared with controls and that IL-12 p40 mRNA, which was present at low levels in controls, was undetectable in unstimulated SLE peripheral blood mononuclear cells (PBMC). Gene expression of IL-12 p35 and p40 was significantly increased in response to SAC, with significantly lower SAC-induced expression of p40 in SLE patients than controls. SAC-stimulated IL-12 p35 and p40 mRNAs were significantly augmented by interferon gamma (IFN-gamma). Exogenous IL-12 or IFN-gamma significantly inhibited IL-10 gene expression, without affecting IL-6 mRNA or other proinflammatory cytokine mRNA levels. These observations were further confirmed by studies of protein production at the single cell level using ELISPOT assay. Downregulation of IL-12 p40 expression appears to be the cause of IL12 p70 deficiency in SLE. If this defect could be repaired, normalization of IL-12 and IFN-gamma production should reduce excessive IL-10 and prevent pathology.
 ...
PMID:Impaired production of IL-12 in systemic lupus erythematosus. III: deficient IL-12 p40 gene expression and cross-regulation of IL-12, IL-10 and IFN-gamma gene expression. 1052 20

After 2 years of steroid therapy that had effectively controlled her systemic lupus erythematosus, a 37-year-old woman presented with fever, erythema (face, upper chest), and low CH50. Increased oral steroid (prednisolone from 15 mg to 40 mg) and intravenous methylprednisolone (mPSL) (80 mg for 3 days) alleviated these symptoms except for the fever. Subsequently, the patient's fever worsened and leukocytopenia, abnormal liver function, lymphadenopathy (neck, axilla), and salivary gland swelling developed. Lymph node histology revealed features characteristic of Kikuchi-Fujimoto's disease (KFD). Laboratory examinations showed WBC 600/microliter, Hb 9.5 g/dl, platelets 90,000/microliter, GOT 766 IU/l, GPT 646 IU/l, LDH 4,228 IU/l, TG 1,622 mg/dl, and ferritin 6,330 ng/ml. Serum interferon gamma was also elevated (673 U/ml). Because a bone marrow smear revealed hemophagocytosis, mPSL pulse therapy (1 g for 3 days) was started for treatment of hemophagocytic syndrome. The fever promptly disappeared, and the patient's clinical symptoms resolved within 2 weeks. The abnormal laboratory data related to KFD and hemophagocytosis returned to normal within 4 weeks after the initiation of mPSL pulse therapy. We speculated that the hemophagocytosis and salivary gland involvement in this patient were also symptoms of KFD. This case indicated that corticosteroid pulse therapy is effective for KFD with serious clinical symptoms.
 ...
PMID:[Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto's disease) accompanied by hemophagocytosis and salivary gland swelling in a patient with systemic lupus erythematosus]. 1069

Gene therapy offers advantages for the immunotherapeutic delivery of cytokines or their inhibitors. After gene transfer, these mediators are produced at relatively constant, non-toxic levels and sometimes in a tissue-specific manner, obviating limitations of protein administration. Therapy with viral or nonviral vectors is effective in several animal models of autoimmunity including Type 1 diabetes mellitus (DM), experimental allergic encephalomyelitis (EAE), systemic lupus erythematosus (SLE), colitis, thyroiditis and various forms of arthritis. Genes encoding transforming growth factor beta, interleukin-4 (IL-4) and IL-10 are most frequently protective. Autoimmune/ inflammatory diseases are associated with excessive production of inflammatory cytokines such as IL-1, IL-12, tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma). Vectors encoding inhibitors of these cytokines, such as IL-1 receptor antagonist, soluble IL-1 receptors, IL-12p40, soluble TNFalpha receptors or IFNgamma-receptor/IgG-Fc fusion proteins are protective in models of either arthritis, Type 1 DM, SLE or EAE. We use intramuscular injection of naked plasmid DNA for cytokine or anticytokine therapy. Muscle tissue is accessible, expression is usually more persistent than elsewhere, transfection efficiency can be increased by low-voltage in vivo electroporation, vector administration is simple and the method is inexpensive. Plasmids do not induce neutralizing immunity allowing repeated administration, and are suitable for the treatment of chronic immunological diseases.
 ...
PMID:Gene therapy of autoimmune diseases with vectors encoding regulatory cytokines or inflammatory cytokine inhibitors. 1095 13

Autoimmune diseases frequently develop as a result of an abnormal activation of autoreactive T cells, excessive production of proinflammatory cytokines, particularly by CD4(+) Th1 cells, and subsequent tissue destruction. Cytokine-dependent immunotherapy can be applied to alter the balance between Th1 and Th2 cell activity, or proinflammatory versus immunosuppressive cytokine profiles. Cytotoxic T lymphocyte (CTL) and/or macrophage activity can also be suppressed. Gene transfer offers numerous advantages for the in vivo delivery of cytokines or their receptors for immunotherapeutic use. We have relied on the injection of naked plasmid DNA into skeletal muscle to deliver therapeutic genes. In particular, we have successfully used this approach to deliver neutralizing cytokine receptors such as interferon gamma (IFNgamma)-receptor-Ig fusion proteins or anti-inflammatory cytokines such as transforming growth factor beta-1 (TGF-beta1) and interleukin 4 (IL-4). Intramuscular gene therapy is effective in protecting against several experimental autoimmune diseases including insulin-dependent diabetes mellitus (IDDM), experimental allergic encephalomyelitis (EAE), and systemic lupus erythematosus (SLE). Another promising approach involves DNA vaccination by plasmid-based codelivery of genes encoding an autoantigen and either a cytokine or other immunomodulatory molecule. Plasmid vectors offer interesting advantages over viral vectors, since they are simple to produce, non-immunogenic and non-pathogenic. They can be repeatedly administered with relatively prolonged periods of expression in vivo, ranging from weeks to months after each injection. Plasmid-based intramuscular gene transfer has great therapeutic potential in the areas of autoimmune and inflammatory disorders.
 ...
PMID:Immune modulation by plasmid DNA-mediated cytokine gene transfer. 1257 Jun 78

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 81C6; Adefovir dipivoxil, Agalsidase alfa, AGM-1470, albumin interferon alfa, alefacept, alosetron hydrochloride, anakinra, anti-CTLA-4 Mab, aprepitant, aripiprazole, atazanavir; BAY-43-9006, BBR-3438, beta-L-Fd4C, bimatoprost, bortezomib, bosentanBR96-doxorubicin; Caspofungin acetate, ciclesonide, cilengitide, cilomilast, COL-1621, COL-3, CpG-7909, cyclosporine; DCVax-Brain, dexmethylphenidate hydrochloride, dexosome vaccine (melanoma), donepezil hydrochloride, drotrecogin alfa (activated), DTI-015, [99Tc]-DTPA-mannosyldextran, duloxetine hydrochloride; Emivirine, emtricitabine, entecavir, epothilone B, estradiol-MNP, etonogestrel/etonogestrel/ethinylestradiol, etoricoxib; Febuxostat, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GVS-111; Heparinase I, HspE7, human alpha-glucosidase, human insulin; Imatinib mesylate, INGN-241, interferon alfa B/D hybrid, interferon alfa Biphasix, ISIS-14803; Lanicemine hydrochloride, 1311-lipiodol, liposome-encapsulated mitoxantrone, lixivaptan, lumiracoxib, lupus-AHP, LY-466700; Marimastat, MEN-10755, micafungin sodium; Nitronaproxen, NSC-683864 Omalizumab, oral insulin; Palonosetron hydrochloride, peginterferon alfa-2a, pimecrolimus, pralnacasan, pramlintide acetate, pregabalin, pyrazoloacridine; R-165335, ranolazine, risperidone, RPR-109881;, RSD-1235, Satraplatin, seocalcitol, sertindole, SMART anti-interferon gamma antibody, sulfasalazine; T-138067, TAK-013, tegaserod maleate, telithromycin, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipifarnib, TP-38; Valdecoxib, vatalanib succinate, voriconazole; ZD-9331.
 ...
PMID:Gateways to clinical trials. 1269 Jul 8


<< Previous 1 2 3 4 5 Next >>