Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004364 (autoimmune disease)
 24,845 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon-alpha (IFN alpha) is the main therapeutic agent in patients infected with the hepatitis C virus (HCV). It is rather safe, but is known to induce the production of autoantibodies and can lead to the occurrence of autoimmune disease. This minireview focuses on the induction of autoimmune thyroid disease (AITD) in HCV-infected patients treated with IFN alpha. Females carry a higher risk to develop AITD upon IFN alpha treatment, with a relative risk of 4.4 (95% confidence interval 3.2-5.9). The presence of thyroid peroxidase antibodies before therapy has a relative risk for AITD of 3.9 (95% confidence interval 1.9-8.1). IFN alpha-associated AITD can consist of autoimmune primary hypothyroidism, Graves' hyperthyroidism, and destructive thyroiditis, with hypothyroidism being the most common side effect. The clear association between AITD and IFN alpha use suggests that high endogenous IFN alpha levels may also be associated with naturally occurring AITD. High endogenous IFN alpha levels are seen in patients infected with certain viruses. It is concluded that IFN alpha is one of the environmental factors capable of triggering the onset of AITD in genetically susceptible individuals.
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PMID:Interferon-alpha and autoimmune thyroid disease. 1293 May 98

IL-18 is now identified as a pleiotropic cytokine that acts as a cofactor for both Th1 and Th2 cell development. Type 1 diabetes is considered a Th1-type autoimmune disease, and to date, the suppressive effect of exogenous IL-18 on the development of diabetes has been reported in 10-wk-old nonobese diabetic (NOD) mice. In the present study we administered exogenous IL-18 systemically in 4-wk-old NOD mice using i.m. injection of the IL-18 expression plasmid DNA (pCAGGS-IL-18) with electroporation. Contrary to previous reports, the incidence of diabetes development was significantly increased in NOD mice injected with pCAGGS-IL-18 compared with that in control mice. Systemic and pancreatic cytokine profiles deviated to a Th1-dominant state, and the the frequency of glutamic acid decarboxylase-reactive IFN-gamma-producing CD4(+) cells was also high in the IL-18 group. Moreover, it was suggested that the promoting effect of IL-18 might be associated with increased peripheral IL-12, CD86, and pancreatic IFN-inducible protein-10 mRNA expression levels. In conclusion, we demonstrate here that IL-18 plays a promoting role as an enhancer of Th1-type immune responses in diabetes development early in the spontaneous disease process, which may contribute to elucidating the pathogenesis of type 1 diabetes.
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PMID:Systemic administration of IL-18 promotes diabetes development in young nonobese diabetic mice. 1463 96

The development of various kinds of autoimmune disease as a result of interferon-alpha (IFN-alpha) therapy has been reported among chronic myeloproliferative disorders(CMPD) including chronic myeloid leukemia(CML). Therefore, we investigated the frequency of autoimmune disorders in 33 patients with hematopoietic diseases treated with IFN-alpha in our department. Thirty-three patients (12 females, 21 males) included cases of CML (n = 23), essential thrombocythemia (ET) (n = 1), multiple myeloma (n = 8), and hypereosinophilic syndrome (HES) (n = 1). Autoantibodies (ANA, dsDNA, and RAPA), thyroid grand functions, and coagulant functions were examined. Twenty-five out of 33 patients were treated with natural IFN-alpha, and 8 patients were treated with recombinant IFN-alpha 2b (rIFN alpha-2b). Three patients were treated with IFN and anticancer agents. Antinuclear antibodies were detected in 2 of 33 patients. RAPA and anti-thyroglobulin antibody became positive in 3 and 4 patients, respectively. Ten patients showed low serum levels of either free T3 and/or free T4. However, none of them showed any clinical symptoms for developing autoimmune diseases. In addition, circulating anticoagulant antibodies were detected in 3 of 23 patients with CML treated with rIFN alpha-2b, but in no cases treated with natural IFN-alpha. Although none of the patients developed autoimmune diseases, we concluded that patients receiving IFN therapy should be carefully monitored for clinical signs and symptoms of autoimmune disorders.
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PMID:[Autoimmune phenomena during interferon-alpha therapy for hematopoietic disorders]. 1465 Sep 58

Alopecia areata is a common type of hair loss. In clinical practice most patients will present with reversible patchy hair loss whereas others may develop complete baldness. Although the etiopathogenesis of alopecia areata is poorly understood, evidence is accumulating that it can be regarded as a T-cell mediated tissue-restricted autoimmune disease of the hair follicle, especially expressing the T-helper-type 1 cytokines interleukin-1beta, interleukin-2, and interferon-gamma. The aim of the study was to compare the serum levels of interferon-gamma in patients with alopecia areata and the control group and also to investigate the difference between the localized form of the disease with the extensive forms like alopecia totalis (AT) and alopecia universalis (AU). Forty patients with alopecia areata and 20 healthy controls were enrolled in the study. Nineteen patients had localized AA (LAA) and twenty-one patients had AT, AU or AT/AU. The serum levels of interferon-y were measured using enzyme immunoassay techniques. The mean serum IFN-gamma level in AA patients (n = 40) was 14.25 +/- 8.76 pg/mL (mean +/- SD), whereas that of LAA (n = 19) or extensive (AT, AU or AT/AU) (n = 21) was 13.45 +/- 6.75 pg/mL or 14.98 +/- 10.37 pg/mL, respectively. The mean serum IFN-gamma level in controls was 9.95 +/- 2.6 pg/mL. Serum levels of IFN-gamma in patients with AA were significantly higher than those in controls (p < 0.05). Significant difference was observed in serum levels of IFN-y between patients with LAA and control group (p < 0.05). Serum levels of IFN-gamma in patients with AT, AU or AT/AU were significantly higher than those in controls (p < 0.05). There was no significant difference in levels of IFN-gamma between patients with LAA and extensive group (p > 0. 05). We conclude that the elevated serum levels of IFN-gamma may reflect the inflammatory symptoms in AA, especially in the extensive form and that control of IFN-gamma production may be important to management of this disease. And also the measurement of serum IFN-gamma in patients with AA may be useful in discriminating those likely to progress to AU from the remaining LAA, or as a prognostic indicator.
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PMID:Interferon-gamma in alopecia areata. 1496 93

Graves' disease (GD) is an autoimmune disorder with genetic predisposition. Interferon-gamma (IFN-gamma) is an important mediator of inflammatory and immune responses. The aim of the present study was to investigate whether the polymorphism of IFN-gamma gene is associated with the development of GD or with clinical course during the antithyroid drug therapy. We have studied the CA repeat polymorphisms in the first intron of IFN gamma gene in Japanese patients with GD (n = 162) and healthy control subjects without antithyroid autoantibodies or family history of autoimmune disorders (n = 133). There was no difference in allele frequency of IFN-gamma gene polymorphism between patients with GD and control subjects. However, the allele 4 (15 CA repeats) frequency was significantly greater in patients whose antithyrotropin receptor antibody (TRAb) became negative within 3 years by antithyroid drug treatment than those with consistently positive TRAb for more than 3 years (34.1% vs. 15.7%, chi2 = 8.545, p = 0.0035, pc = 0.049). The in vitro production of IFN-gamma by concanavalin A-stimulated peripheral blood mononuclear cells was significantly smaller in control subjects with the allele 4 compared to those with the other alleles. In conclusions, the CA repeat polymorphism of the IFN-gamma gene might be associated with the outcome of anti-thyroid drug treatment.
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PMID:A polymorphism of interferon-gamma gene associated with changes of anti-thyrotropin receptor antibodies induced by antithyroid drug treatment for Graves' disease in Japanese patients. 1506 23

We have shown that neutralization of IFN-inducible protein 10/CXCL10, a chemokine for Th1 cells, breaks Th1 retention in the draining lymph nodes, resulting in exacerbation in Th1-dominant autoimmune disease models induced by immunization with external Ags. However, there have been no studies on the role of CXCL10 neutralization in Th1-dominant disease models induced by constitutive intrinsic self Ags. So, we have examined the effect of CXCL10 neutralization using a type 1 diabetes model initiated by developmentally regulated presentation of beta cell Ags. CXCL10 neutralization suppressed the occurrence of diabetes after administration with cyclophosphamide in NOD mice, although CXCL10 neutralization did not significantly inhibit insulitis and gave no influence on the trafficking of effector T cells into the islets. Because both CXCL10 and CXCR3 were, unexpectedly, coexpressed on insulin-producing cells, CXCL10 was considered to affect mature and premature beta cells in an autocrine and/or paracrine fashion. In fact, CXCL10 neutralization enhanced proliferative response of beta cells and resultantly increased beta cell mass without inhibiting insulitis. Thus, CXCL10 neutralization can be a new therapeutic target for beta cell survival, not only during the early stage of type 1 diabetes, but also after islet transplantation.
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PMID:CXC chemokine ligand 10 neutralization suppresses the occurrence of diabetes in nonobese diabetic mice through enhanced beta cell proliferation without affecting insulitis. 1555 99

The interferon-gamma (IFN-gamma)/interleukin-12 (IL-12) pathway is a pivotal player in the immune system and is central to controlling mycobacterial infections. We highlight the most recent and relevant advances in understanding this pathway and their repercussions on basic and clinical science. Human mutations in IFN-gamma receptor-1 (IFN-gammaR1), IFN-gammaR2, IL-12p40, IL-12 receptor-beta1, signal transducer and activator of transcription-1, and nuclear factor-kappaB essential modulator are analyzed in the context of genetic susceptibility to mycobacterial diseases. A diagnostic and therapeutic approach is described. The IFN-gamma/IL-12 pathway is central in immune control of both environmental and autochthonous challenges, as reflected in human mutations and animal models. Besides being crucial for mycobacterial control, the IFN-gamma/IL-12 pathway is also involved in the pathogenesis of autoimmune disease as well as tumor development and control. Genotype-phenotype correlations have been established for certain genes in this pathway, some of which have therapeutic implications.
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PMID:Defects in the interferon-gamma and interleukin-12 pathways. 1566 Oct 20

Cytokines, most particularly TNF and type I IFN (IFN-alphabeta), have been long considered essential elements in the development of autoimmunity. Identification of TNF in the pathogenesis of rheumatoid arthritis and TNF antagonist therapy represent successes of immunology. IFN-alphabeta plays a major role in systemic lupus erythematosus (SLE), a prototype autoimmune disease characterized by a break of tolerance to nuclear components. Here, we show that TNF regulates IFN-alpha production in vitro at two levels. First, it inhibits the generation of plasmacytoid dendritic cells (pDCs), a major producer of IFN-alphabeta, from CD34+ hematopoietic progenitors. Second, it inhibits IFN-alpha release by immature pDCs exposed to influenza virus. Neutralization of endogenous TNF sustains IFN-alpha secretion by pDCs. These findings are clinically relevant, as five of five patients with systemic juvenile arthritis treated with TNF antagonists display overexpression of IFN-alpha-regulated genes in their blood leukocytes. These results, therefore, might provide a mechanistic explanation for the development of anti-dsDNA antibodies and lupus-like syndrome in patients undergoing anti-TNF therapy.
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PMID:Cross-regulation of TNF and IFN-alpha in autoimmune diseases. 1572 81

Mice with a deficiency in IFN-gamma or IFN-gamma receptor (IFN-gammaR) are more susceptible to collagen-induced arthritis (CIA), an experimental autoimmune disease that relies on the use of complete Freund's adjuvant (CFA). Here we report that the heightened susceptibility of IFN-gammaR knock-out (KO) mice is associated with a functional impairment of CD4+CD25+ Treg cells. Treatment of wild-type mice with depleting anti-CD25 antibody after CFA-assisted immunisation with collagen type II (CII) significantly accelerated the onset of arthritis and increased the severity of CIA. This is an indication of a role of Treg cells in the effector phase of CIA. IFN-gammaR deficiency did not affect the number of CD4+CD25+ T cells in the central and peripheral lymphoid tissues. In addition, CD4+CD25+ T cells isolated from naive IFN-gammaR KO mice had a normal potential to suppress T cell proliferation in vitro. However, after immunisation with CII in CFA, the suppressive activity of CD4+CD25+ T cells became significantly more impaired in IFN-gammaR-deficient mice. Moreover, expression of the mRNA for Foxp3, a highly specific marker for Treg cells, was lower. We further demonstrated that the effect of endogenous IFN-gamma, which accounts for more suppressive activity in wild-type mice, concerns both Treg cells and accessory cells. Our results demonstrate that the decrease in Treg cell activity in CIA is counter-regulated by endogenous IFN-gamma.
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PMID:Defective CD4+CD25+ regulatory T cell functioning in collagen-induced arthritis: an important factor in pathogenesis, counter-regulated by endogenous IFN-gamma. 1574 88

Because low-dose interferon-alpha (IFN-alpha) treatment had proved effective in several models of chronic inflammation and autoimmune disease, a possible role of IFN-alpha in modulating the response of swine leukocytes to bacterial endotoxin was investigated in this study. Exposure of swine peripheral blood mononuclear cells (PBMC) to low concentrations of human IFN-alpha caused a strong, dose-dependent decrease in CD14 expression, the lowest level being observed at 5 U/ml IFN-alpha. This result was confirmed if PBMC were later exposed to purified lipopolysaccharide (LPS). A 10-fold lower IFN-alpha concentration (0.5 U/ml) caused the largest reduction of tumor necrosis factor-alpha (TNF-alpha) accumulation in the medium of pulmonary alveolar macrophages (PAM), stimulated with bacterial LPS. At 0.5 U/ml, the expression of the TNF-alpha gene in PAM was also strongly reduced, as opposed to cells pretreated with 50 U/ml IFN-alpha. In contrast, expression of the interleukin-1beta (IL- 1beta) gene was stimulated and that of the IL-6 gene was not significantly affected at both IFN-alpha concentrations. Results point to an important role of IFN-alpha in control of the inflammatory response to bacterial endotoxin in pigs.
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PMID:Effects of IFN-alpha on the inflammatory response of swine leukocytes to bacterial endotoxin. 1581 46


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