ABSTRACT
Previous studies of an experimental human immunoglobulin preparation for intravenous use, containing normal pooled IgM (IVIgM), have shown its beneficial therapeutic effect in experimental autoimmune diseases. The mechanisms of its immunomodulatory activity remain however, poorly understood. In the experiments reported here, IVIgM inhibited the proliferation of various autonomously growing human lymphoid cell lines in vitro, as well as of MLR- and of PHA-stimulated human T-lymphocytes. These effects of IVIgM were observed at non-apoptotic concentrations and were stronger on a molar basis than those of normal pooled IgG for intravenous use (IVIg). Both preparations, when administered to SCID mice, repopulated with human peripheral blood mononuclear cells, delayed the expression of the early activation marker CD69 on both human CD4+ and CD8+ T-lymphocytes, activated by the mouse antigenic environment. The data obtained show that normal pooled human IgM exerts a powerful antiproliferative effect on T-cells that is qualitatively similar but quantitatively superior to that of therapeutic IVIg. Our results suggest that infusions with IVIgM might have a significant beneficial immunomodulating activity in patients with selected autoimmune diseases.
Subject(s)
Immunoglobulin M/administration & dosage , Immunoglobulins, Intravenous , T-Lymphocytes/immunology , Animals , Antigens, CD/analysis , Apoptosis/drug effects , Biomarkers/analysis , Cell Line , Cell Proliferation/drug effects , Cells, Cultured , Female , Flow Cytometry , Fluorescent Antibody Technique , Humans , Immunosuppression Therapy , Lymphocyte Activation/drug effects , Mice , Mice, SCID , Phosphatidylserines/analysisABSTRACT
A major event in the pathogenesis of systemic lupus erythematosus (SLE) is the breaking of tolerance to native DNA and the appearance of IgG anti-double-stranded (ds) DNA antibodies. The mechanisms of the losing of tolerance are not well understood. Continuous efforts have been made in the past to induce anti-native DNA IgG autoantibodies in non-autoimmune animals but the relevance of the approaches used to what happens in spontaneous disease is unclear. We succeeded in breaking tolerance to native DNA in nonautoimmune-prone BALB/c mice by immunization with natural DNA/protein complexes. These complexes included nucleosomes, crude commercial histone and nucleohistone preparations. The anti-dsDNA IgG response lasted for more than an year. IgG deposition in the kidneys of the animals was repeatedly shown. As DNA-specific B cells behave in many ways as non-autoreactive B cells, we suggest that the activity of the self-reactive B lymphocytes could be selectively inhibited in a way that mimics a physiological mechanism controlling the magnitude and duration of the IgG antibody response to foreign antigens.
Subject(s)
Antibodies, Antinuclear/blood , DNA/immunology , Histones , Immunization/methods , Nucleosomes , Protein Precursors , Ubiquitins , Animals , Female , Immunoglobulin G/blood , Mice , Mice, Inbred BALB C , Mice, Inbred MRL lpr , Self ToleranceABSTRACT
Steroid esters of cynnamic acid derivatives have been synthesized by a heterogeneous Wittig reaction under sonochemical conditions from the corresponding triphenylphosphonium bromides and unprotected phenolic aldehyds using K2CO3 as a base. 5 beta-Cholan-3 alpha, 7 alpha, 12 alpha, 24-E-ferulate (11') exhibited a marked inhibitory effect on influenza virus A. The synthetic 3 alpha, 24-E-diferulates of 5 beta-cholan-3 alpha, 24- diol, 5 beta-cholan-3 alpha, 12 alpha, 24-triol and 5 beta-cholan-3 alpha, 7 alpha, 12 alpha, 24-tetrol (8, 9 and 12) showed antitumor activity on leukemia P-388 in mice.
Subject(s)
Antineoplastic Agents/chemistry , Antiviral Agents/chemistry , Cholic Acids/chemistry , Cinnamates/chemistry , Cinnamates/therapeutic use , Leukemia P388/drug therapy , Viruses/drug effects , Animals , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/toxicity , Antiviral Agents/pharmacology , Cell Line , Cinnamates/toxicity , Influenza A virus/drug effects , Male , Mice , Mice, Inbred DBA , Microbial Sensitivity Tests , Molecular Structure , Nuclear Magnetic Resonance, BiomolecularABSTRACT
Primary screening of alcohol extracts of fruits of Maclura aurantiaca (Moraceae) and the overground part of Epilobium hirsutum (Onagraceae) was conducted in order to test the anti-tumour action on models in mice. Applied in doses of 100 mg/kg and 90 mg/kg, Maclura extract increased the life span of the mice by 158 and 152% accordingly in leucosis P-388 and ascitic tumour of Ehrich. In doses of 1 mg/kg and 3 mg/kg the Epilobium extract prolonged the life span of the mice by 156 and 158% accordingly in leucosis P-388 and ascitic tumour of Ehrlich.
