CONTENTS
Review
- The Immunological Basis of Current and Novel Therapies of Multiple Sclerosis
BENEDICTE DUBOIS and GHISLAIN OPDENAKKERAbstract. The etiology and the pathogenesis of multiple sclerosis are not yet known. There might be a role for genetic susceptibility, for environmental factors and for inflammatory and immunological changes. Most of the actual therapies are based on the latter two phenomena. We review here corticosteroids, interferon ß and copolymer 1 as the current drugs of choice and compare schematically the immunological basis of the mechanisms of action of these three substances with those of experimental or other treatments.
Keywords: multiple sclerosis; therapy; immunological network; interferon ß; copolymer 1; corticosteroids.
Full-textPDF download - Superantigens and Their Role in Autoimmune Disorders
JOEL SCHIFFENBAUERAbstract. The ability of superantigens to activate large numbers of T cells suggests that they may play a role in the course of autoimmune disorders Data from several animal models of autoimmune disorders including experimental allergic encephalomyelitis and collagen induced arthiritis supports this hypothesis. Administration of bacterial superantigens can induce an exacerbation of the autoimmune process in these models, or induce disease de novo in the appropriately immunized animal. Studies of several human disorders including rheumatoid arthiritis, Kawasaki disease, insulin-dependent diabetes, and psoriasis lend credence to the concept that bacterial superantigens may play a role in the pathogenesis of these diseases. Nevertheless, in some cases, depending on the timing of administration and the model, superantigens may lead to an amelioratiom of the autorimmune process. Based on these results in seems logical to conclude that superantigens can have a significant impact on the course of the immune and autoimmune mediated disorders.
Keywords: superantigen; staphylococcal enterotoxin; autoimmune; experimental allergic, encephalomyelitis.elitis.
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- Koch’s Postulates and Autoimmunity: an Opposing Viewpoint
CHAIM PUTTERMAN and YAAKOV NAPARSTEKAbstract. Autoimmunity is characterized as a state of abnormal specific humoral and cell-mediated responses against constituents of body tissues. One time- honored approach to explaining the pathogenesis of autoimmunity has been application of the Koch’s postulates, on loan from the field of microbiology suggesting that autoantibodies and/or autoreactive T cells are the presumed “ pathogens” of autoimmunity, and that passive transfer of these autoimmune factors to susceptible animals will result in the induction of the autoimmune disease. We suggest that autoimmunity is not in many cases due to the presence of factors leading to the autoimmune response in those susceptible. Instead, it is the lack of a factor which leads to the development of autoimmunity, a factor (cytokine, protein, gene, etc.) which is present in the healthy individual and normally protects in from disordered immune regulation. We propose to direct more research into therapeutic modulation of autoimmunity by administration of putative “protective factors”, rather than by attempts to depress or remove autoreactive cells and antibodies from the autoimmune.
Keywords: autoimmunity; autoantibodies; autoreactive cells; pathogenesis.enesis.
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- Gene Therapy for Autoimmune Demyelinating Disease of the Central Nervous System
PETER M. MATHISEN and VINCENT K. TUOHYAbstract. Gene therapy is currently being explored as a new therapeutic treatment of autoimmune disease. The genetic modification of autoreactive memory T cells ( T cell- mediated gene therapy) and autoimmune target tissue ( target tissue gene therapy) to produce immunoregulatory cytokines offers a promising way to regulate autoimmunity. Furthermore, regenerative gene therapy offers the possibility of delivering growth factors to damaged autoimmune target tissue as a way of mediating repair. In the current review we discuss the different experimental models that are being used to test the efficacy of gene therapy in that treatment of autoimmune disease. We also discuss the importance of regulating transgene expression to ensure the therapeutic transgene products are delivered specifically to the autoimmune milieu in an antigen- inducible, non-constitutive manner.
Keywords: gene therapy; autoimmune disease; myelin; inerleukin 10; interleukin 4; cytokines; growth factors.actors.
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- Decrease of Enhanced Interferon a Levels in Sera of HIV-Infected and AIDS Patiens Receiving Combined Antiretroviral Therapy
EGBERT PIASECKI, BRYGIDA KNYSZ, JACEK GĄSIOROWSKI and ANDRZEJ GŁADYSZAbstract. In the advanced stages of human immunodeficiency virus (HIV) infection the defective interferon (IFN) responses have been observed. Persisting high lebels of the acid-labile interferons (al-IFNs) have been found in sera of the patients with AIDS. The combined antiretroviral therapy, that included the reverse transcriptase and viral protease inhibitors, resulted in a significant improvement of the clinical state of the majority of HIV-infected patients. In this report we describe the levels of IFNs in 41 HIV patients subjected to the combined treatment. High IFN levels (median 84, up to 576 U/ml) were found in sera of patients classified as the stage C2 or C3 of AIDS before the treatment. The combined therapy resulted in the decrease of IFN levels (median 7.5, up to 24 U/ml) that approached the levels of IFNs detected in the HIV+, A1-A3 stage patients (median 4, up to 36 U/ml). In contrast, the unsuccessful therapy connected with the worsening of the clinical state and the the decrease of CD4+ cell count had no effect on the IFNs level (median 48, up to 96 U/ml). Thus, the measurements of IFN activity in sera may be useful for monitoring the effects of the antiretroviral combined therapy. In sera of the AIDS patients, subjected to the antiviral bioassays, the mixture of the acid-labile and acid-atable form of IFN-a, with the prevailing al-IFN-a, have been detected.
Keywords: interferon a; acid-labile interferon (al-IFN); al-IFN-a, AIDS, HIV-infected patients, combined antiretroviral therapy.
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- In Vitro Secretion of Interleukin 2 and Expression of IL-2 Receptor in Peripheral Blood Lymphocytes in High Risk of Insulin-Dependent Diabets Mellitus Subjects
ADAM KRĘTOWSKI, JANUSZ MYŚLIWIEC, MAŁGORZATA SZELACHOWSKA, CEZARY BRZOZOWSKI, MIROSŁAWA PIETRUCZUK and IDA KINALSKAAbstract. Interleukin 2 (IL-2) – a Th1 lymphocyte-derived cytokine is at present considered to play an important role in etiopathogenesis of insulin-dependent diabetes mellitus. In the previous studies increased, decreased and unchanged IL-2 levels in patients with recent onset of insulin-dependent diabetes mellitus (IDDM) were found. These differences could be a result of different metabolic status or/and a different stage of the autoimmune process. The aim of our study was to estimate in vitro secretion of IL-2 and CD25 antigen expression by the peripheral blood T lymphocytes in subjcts at the preclinical stage of IDDM (prediabetes), but still without metabolic disturbances. In 27 first degree relatives of IDDM patients with antibodies against ifferent pancreatic islet cell antigens (ICA, GADA, IAA, IA-2) CD25 antigen expression on peripheral blood lymphocytes T was measured by flow cytometry and IL-2 concentration in supernatants of 48 and 72 h cultures of peripheral whole blood with 10 m g/ml PHA was estimated by ELISA. The control group was comprised of 34 age and sex-matched healthy volunteers. In the studied high risk IDDM subjects the decreased CD25 expression in peripheral CD4+ lymphocytes T and a negative correlation between the percentage of CD25+ cells and islet cell antibodies (ICA) titres was observed. No differences in IL-2 levels in supernatants of 48 h and 72 h blood cultures was found in subjects with single antibody (ICA+) in comparison to healthy controls. A significant increase of IL-2 secretion at 72 h of PHA stimulation was shown in first degree relatives of IDDM patients with a combination of 3 or more antipancreatic-B cell antibodies.There were also a significant negative correlation between glutamic acid decarboxylase antibodies (GADA) titres and IL-2 levels in 72 h of culture. The present study suggests the involvement of IL-2 in the pathogenesis of IDDM. The estimation of CD25 antigen expression in the peripheral blood lymphocytes could be an additional immunological marker of identification of subjects in prediabetes.
Keywords: interleukin 2; CD25 antigen; diabetes mellitus type 1; etiopathogenesis.
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- Capability of Adriamycin and Busulfan to Induce Adaptive Response in Vitro
ELŻBIETA L. ANUSZEWSKA and JADWIGA H. KOZIOROWSKAAbstract. The capability to induce an adaptive response by low doses of busulfan (BS) or adriamycin (ADR) was studied in two kinds of mammalian cells with acquired or inherent resistance to ADR (ME!*/R and V3) cultured in vitro. The results indicate the presence of an adaptive responce to ADR in both kinds of used cells pretreated with a low priming dose of ADR. In the same kind of cells no adaptive response to BS priming with a low dose of this drug was found.
Keywords: adriamycin; busulfan; adaptive response.
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- HLA-A, B, C Antigens in Pulmonary Sarcoidosis in Polish Population
ANNA DUBANIEWICZ and ZOFIA SZCZERKOWSKAAbstract. The aim of this study was to analyze association between HLA class I antigens and sarcoidosis in Poland. HLA-A,B, C antigens in a group of 100 patients suffering from sarcoidosis and in group of 100 healthy blood donors were determined. Histocompability typing was performed by the NIH method using commercially available sera. For statistical analisys c 2 test was used after Yates’ correction. The relative risk was calculated by Woolf’s method. We found that HLA-B8 and -Cw7 prevalence was significantly higher in patients with sarcoidosis than in healhy controls. HLA-B35, -B40, -B40, -Cw2 and -Cw4 antigen expression was significantly lower in pulmonary sarcoidosis than in the tested group of healthy individuals. The highest relative risk of sarcoidosis was connected with HLA-B8 and -Cw7. The results obtained suggest that, in the population suffering from pulmonary sarcoidosis in nothern Poland, as compared with the control group of healthy persons, antigens HLA-B8 and -Cw7 are significantly more frequent. It can be assumed that, the presence of these antigens may be connected with a greater risk of pulmonary sarcoidosis. In the group of patients, as compared with the control population, the occurrnce of antigens HLA_B35, -B40, -Cw2 and -Cw4 is significantly more rare.
Keywords: HLA-A, B, C; pulmonary sarcoidosis.
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- Effect Of Granulocyte Colony Stimulating Factor Treatment on ex Vivo Cytokine Production by Blood Cells of Patients after Chemotherapy or Radiotherapy
TERESA KAMIŃSKA, ANNA DMOSZYŃSKA, IWONA HUS, ADAM WALTER CRONECK and MARTYNA KANDEFER-SZERSZEŃ
Abstract. We explored ex vivo alterations in the cytokine release of stimulated blood cells taken from 8 patients with hematological malignancies who, after chemotherapy or radiotherapy developed leukopenia, and were treated for 3-7 days subcutaneously with granulocyte colony stimulating factor (G-CSF), daily, dose of 5 m g/kg of body weight. Blood was also taken from 8 heathy controls not treated with G-CSF and from patients before and 24 h after last dose of G-CSF and ex vivo treated with interferon (IFN) inducers: Newcastle disease virus (NDV), phytohemaagglutinin (PHA), concanavalin A (Con A) and with tumor necrosis factor (TNF) inducer – lipopolysaccharide (LPS). Blood cells of patients before G-CSF treatment exhibited ex vivo a low ability was detected. We conclude that G-CSF treatment for 3-7 days does not only increase the number of white blood cells (WBC) and neutrophilic granulocytes but also modify the host response of patients with hematological malignancies to microbial infections.
Keywords: recombinant human colony stimulating factor; interferons; tumor necrosis factor.