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)

The present study was designed to evaluate the therapeutic activity of a novel immunosuppressive agent, deoxyspergualin (DSG, NKT-01) in male MRL/MpJ-lpr/lpr (MRL/lpr) mice suffering advanced systemic lupus erythematosus (SLE)-like lesions. Treatment with DSG in the early phase of the disease at doses of 1.5 and 3 mg/kg strongly suppressed the development of SLE-like lesions. When DSG was administered from week 21 through 29 to MRL/lpr mice in advanced phases of the disease, a daily iv dose of 3 mg/kg (5 days/week) markedly reduced the symptoms, whereas a dose of 1.5 mg/kg did not. Moreover, DSG treatment at a dose of 3mg/kg, started at the time when the blood urea nitrogen levels were over 50 mg/deciliter, significantly prevented deterioration of the hyperuremia. Taking these findings into consideration, DSG was found to be a promising agent for curing such established autoimmune disease.
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PMID:Deoxyspergualin therapy in autoimmune MRL/1pr mice suffering advanced lupus-like disease. 227 76

We investigated the effect of spergualin (SGL) upon the development of spontaneous systemic lupus erythematosus-like lesions in male MRL/MpJ-lpr/lpr mice. SGL was administered ip at doses of 2.5, 5 and 10 mg/kg to two groups of mice. One group received SGL prophylactically from 7 to 21 weeks of age. The other group received SGL curatively from 13 to 27 weeks of age. The occurrence of lupus lesions was characterized by enlarged lymphoid organs, high anti-DNA titer and blood urea nitrogen, and severe glomerular nephritis. In both groups these characteristics were significantly suppressed by SGL in a dose-dependent manner. This inhibitory activity was greatest at a dose of 10 mg/kg. These findings suggest that SGL has prophylactic and curative effects against lupus lesions in autoimmune disease in mice.
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PMID:Effect of spergualin in autoimmune disease mice. 368 10

MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop an autoimmune disease characterized by anti-DNA antibodies, immune-complex glomerulonephritis, and massive proliferation of a distinct population of T cells. The proliferating T cells have the phenotype Thy-1.2+, T200+, Lyt-1+,2-,3-, but Thy-1.2 and Lyt-1 are expressed in abnormally low density. These cells appear to function as helper cells, and neonatal thymectomy prevents both lymphoproliferation and autoimmunity, which suggests that autoimmunity in MRL/lpr mice is secondary to T cell proliferation. We therefore attempted to reduce lymphoproliferation by treating MRL/lpr mice with a single injection of rat monoclonal antibody (MAb) to Thy-1.2 (30-H12, IgG2b). Mice were treated at 8 wk, before the onset of overt disease. We found that MRL/lpr mice were resistant to depletion of circulating T cells (CTC) by anti-Thy-1.2; 0.6 mg of antibody totally depleted CTC from normal mice, but had little or no effect on CTC in MRL/lpr mice. However, treatment with 6 mg of MAb against Thy-1.2 reduced CTC in MRL/lpr mice by over 70%. Moreover, this single treatment markedly reduced the proliferation of CTC over the ensuing 3 mo, despite clearance of the anti-Thy-1.2 from the circulation within 3 wk. Treated mice maintained better renal function than untreated controls, as assessed by levels of blood urea nitrogen (BUN), although anti-DNA antibodies were not significantly reduced. The effect of anti-Thy-1.2 was specific; treatment with rat MAb to the common leukocyte antigen T200 produced only a transient effect on circulating lymphocytes and did not reduce renal disease. The prolonged effects of a single injection of anti-Thy-1.2 suggest that the MAb produces a sustained alteration in immune regulation. The improvement in renal disease is in accord with evidence that autoimmune disease in MRL/lpr mice is T cell dependent. Monoclonal anti-lymphocyte antibodies may be useful in the treatment of autoimmunity.
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PMID:Treatment of autoimmune MRL/Ipr mice with monoclonal antibody to Thy-1.2: a single injection has sustained effects on lymphoproliferation and renal disease. 618 19

Conflicting data on subpopulations of peripheral blood lymphocytes in patients with autoimmune disease largely reflect variations in methods of study. An investigation was therefore conducted aimed at avoiding this difficulty. Serial samples of peripheral blood mononuclear cells from 42 patients with hyperthyroid Graves' disease were collected at monthly intervals before, during, and for 12 months after a six month course of carbimazole. Samples were stored in liquid nitrogen until completion of the study, when they were thawed and all samples from each patient analysed within the same assay using mouse monoclonal antibodies to human cell subsets and a fluorescence activated cell sorter. Proportions of cytotoxic/suppressor (OKT8) positive cells before treatment (mean 17.4 (SEM 0.8)%) were significantly lower (p less than 0.001) than those in normal controls (29.8 (1.9)%; n = 10) and returned to normal by the end of treatment. In contrast, the proportions of activated T cells (OKIa-OKM1) were significantly raised before treatment as compared with normal (14.4 (0.6)% versus 4.6 (0.8)%; p less than 0.001) and fell to normal by the end of treatment. Proportions of OKT3 and OKT4 positive T cells remained unchanged throughout treatment and in the succeeding 12 months. In patients who relapsed after treatment there was a rise in the proportion of activated T cells and a fall in OKT8 positive T cells, which returned towards normal with retreatment. The explanation for the alterations in numbers of circulating T cells remains to be determined but they may provide a means for predicting more accurately the outcome of Graves' disease after treatment with carbimazole.
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PMID:Analysis of T cell subsets in Graves' disease: alterations associated with carbimazole. 642 64

Peritoneal macrophages from experimental autoimmune prostatitis (EAP) rats were examined for their capacity to secrete reactive nitrogen intermediates (RNI), measured by the release of nitrite (NO2-). Under basal conditions, there was a significant increase of NO2- secretion by cells from autoimmune rats in relation to resident cells. After stimulation in vitro with lipopolysaccharide (LPS), the NO2- production was higher in cells from autoimmune rats compared to treated and nontreated controls. The NO2- production was dependent upon the presence of L-arginine in the culture medium. The addition of L-NG-monomethyl arginine, an inhibitor of nitric oxide synthesis, to the medium reduced the amount of measurable NO2-. Kinetic studies in cells from EAP rats showed that in basal conditions there was an significant release of NO2- at day 7 of immunization that was maintained during the whole period studied. After LPS stimulation, there was a similar behavior and maximum values were reached at day 28 of immunization. These results, together with the lesion observed in the prostate gland, suggest that RNI may be of pathogenic importance in the development of early tissue inflammation and autoimmune disease of the prostate.
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PMID:Production of reactive nitrogen intermediates (RNI) by peritoneal macrophages from rats with experimental autoimmune prostatitis (EAP). 755 47

Long-term treatment with dimethylthiourea (DMTU), a scavenger of hydroxyl radical (.OH) and hypochlorous acid (HOCl), suppressed the age-related development of autoimmune disease in NZB x NZWF1 mice. Treatment reduced autoantibody production, retarded increase in blood urea nitrogen, and prolonged life. The results suggest that .OH and HOCl may, at least in part, enhance the development of autoimmune diseases in NZB x NZWF1 mice.
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PMID:Long-term treatment with dimethylthiourea inhibits the development of autoimmune disease in NZB x NZWF1 mice. 759 64

In the New Zealand black (NZB) x New Zealand white (NZW) (B/W) mouse model of systemic lupus erythematosus (SLE), females die prematurely and males have late onset of disease. It has been proposed that testosterone protects B/W mice from rapidly progressive SLE. The mechanisms of androgenic suppression of the immune system, however, are not understood. We tested the hypothesis that testosterone exerts protective effects in males through classic receptor-mediated actions. Flutamide, a potent and specific androgen receptor blocker, was administered continuously to B/W mice from 6 weeks of age, and the animals were monitored in a longevity study. Our supposition that flutamide treatment would accelerate disease was upheld in female B/W mice. In females, flutamide clearly accelerated mortality and reduced longevity to (median) 30 weeks as compared with 37 weeks in controls (p = 0.003). In male B/W mice, mortality was identical in treated and control animals in the early phase of the study, and deleterious effects of treatment were apparent only after the first year of treatment. Flutamide-treated males had significant elevation of serum testosterone, but their atrophied seminal vesicles strongly suggested that peripheral androgen effects were blocked. Albuminuria, blood urea nitrogen, and anti-DNA antibodies were not altered by flutamide in females or males. The receptor-mediated effects of androgens on murine autoimmune disease were dependent on gender and were noted primarily in females and in males that survived past 1 year of age.
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PMID:Accelerated deaths from systemic lupus erythematosus in NZB x NZW F1 mice treated with the testosterone-blocking drug flutamide. 808 83

Lewis rats undergo a relapsing paralytic disease upon challenge with spinal cord emulsified in complete Freund's adjuvant (CFA). Treatment with two intracardiac injections of liposomes composed of whole myelin significantly reduced the severity of disease. Protection was disease-specific since treatment with myelin liposomes did not protect Lewis rats against adjuvant arthritis (AA), a CNS-unrelated T-cell-mediated autoimmune disease. Myelin-liposome-treated, spinal cord/CFA-immunized rats displayed borderline reduction of delayed-type hypersensitivity (DTH) (ear swelling) reactions to myelin and myelin basic protein (MBP), but significantly reduced in vitro lymphnode cell proliferation in response to these antigens. Responses to purified protein derivative of Mycobacterium tuberculosis (PPD) were not reduced, emphasizing the antigen-specific nature of the myelin-liposome-mediated suppression. Spleen cell proliferative responses were inconsistent and often poor. However, when cultured in the presence of NG-monomethyl-L-arginine (MMA), antigen-specific proliferation of spleen cells from both treated and control rats was greatly enhanced, indicating that reactive nitrogen intermediates contributed to the decrease in spleen cell proliferation. Purified splenic T cells from treated rats displayed a pattern of proliferation similar to that of unseparated lymphnode cells. Treatment of rats with a single injection of myelin liposomes after recovery from the first clinical episode significantly reduced the severity of the relapses.
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PMID:Myelin-liposome protection against experimental autoimmune encephalomyelitis is associated with reduced neuroantigen-specific T-cell-mediated responses. 842 33

The effects of airborne pollutants on the immune system have been most widely studied in the respiratory tract. Entry may occur as a volatile gas (ozone, benzene), as liquid droplets (sulfuric acid, nitrogen dioxide), or as particulate matter (diesel exhaust, aromatic hydrocarbons). The subsequent interaction with the immune system may result in local and systemic responses, and studies have shown examples of disease occurring from both overactive immune responses and immunosuppression. For the most part, airborne pollutants (small molecular weight chemicals) have to be coupled with other substances (proteins or conjugates) before they can be recognized by the immune system and exert their effects. Fortunately, this encounter rarely causes immunologically mediated human disorders. The following briefly reviews some of the disorders that may occur. Immunologically nonspecific inflammation of the lung can occur after inhalation of ozone in anyone given sufficient dose and time of exposure. Immunologically specific cell-mediated (T lymphocyte) reactions appear to predominate in chronic beryllium disease, which results in a granulomatous form of lung disease. Beryllium alone does not appear to be antigenic but requires chemical linkage with a larger molecule. Mercury-induced autoimmune disease (immune system attacks self-antigens) affecting kidneys and lungs has been demonstrated in animal models (changes similar to those seen in people with Goodpasture's syndrome). Immunosuppression can be demonstrated after exposure to polycyclic aromatic hydrocarbons (2,3,7,8-tetrachlorodibenzo-p-dioxin). Hypersensitivity (or allergic) reactions can occur after exposure to toluene diisocyanate (occupational asthma). In summary, airborne pollutants may cause a wide spectrum of immunologically mediated disorders. There is clearly an underlying genetic basis for the susceptibility to immunologic disease resulting from exposure to pollutants, but knowledge in this area is rudimentary at present. Studies have been impeded by lack of appropriate in vitro models, as well as difficulties in identifying the biologically active substance.
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PMID:Airborne pollutants and the immune system. 863 40

Autoimmune disease is generally rare in tropical rural populations. Plasma concentrations of nitrite plus nitrate (reactive nitrogen intermediates), reflecting high nitric-oxide production somewhere in the body, can be high in patients who have cerebral malaria, but even higher in symptom-free parasitised individuals, who are termed malaria-tolerant. We propose that the nitric oxide causing high serum levels of reactive nitrogen intermediates in malaria-tolerant individuals is generated in macrophages during the establishment and maintenance of malarial tolerance, and makes autoimmune disease rare in many tropical rural populations by minimising proliferation of autoreactive T cells. Conversely, innately low levels of nitric-oxide generation in these populations, selected by malarial disease in tropical areas, could rationalise their high frequency of autoimmune disease and hypertension when living in western societies.
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PMID:Does malarial tolerance, through nitric oxide, explain the low incidence of autoimmune disease in tropical Africa? 902 7


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