ABSTRACT
Immunotherapy with Interferon-beta (IFNbeta) results in remarkably beneficial effects in patients with relapsing-remitting multiple sclerosis (MS), although the mechanisms by which it exerts these beneficial effects remain poorly understood. An investigation was made of the effects of IFNbeta on pro-inflammatory and anti-inflammatory cytokine production in peripheral blood cells in MS patients, both untreated and those undergoing immunotherapy, as well as in healthy controls. Results show a significant increase in the production of pro-inflammatory cytokines such as TNFalpha, IFNgamma and IL-12 in the plasma and in the supernatant of leukocyte cultures from MS patients with the untreated disease; IFNbeta administration significantly reduced the levels of TNFalpha and IFNgamma, with no changes in the level of IL-12. The Interferon-beta therapy also led to a significant increase in the production of IL-10, as well as a slight increase in that of TGFbeta. The reduction in pro-inflammatory cytokine production in the treated MS patient group, accompanied by a simultaneous increase in the production of anti-inflammatory cytokines and the reduction of relapse rates suggests that the beneficial effects of IFNbeta immunotherapy result, at least in part, from the modulation of cytokine patterns.
Subject(s)
Immunotherapy , Interferon-beta/metabolism , Interferon-gamma/metabolism , Multiple Sclerosis/immunology , Neutrophils/metabolism , Adolescent , Adult , Brazil , Female , Humans , Interferon-beta/immunology , Interferon-gamma/immunology , Interleukin-10/metabolism , Interleukin-12/metabolism , Male , Middle Aged , Multiple Sclerosis/blood , Multiple Sclerosis/physiopathology , Multiple Sclerosis/therapy , Neutrophils/immunology , Neutrophils/pathology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Most reports of autoimmune response during infection with the parasite Trypanosoma cruzi have dealt with the cardiomyopathic form of Chagas' disease, but little is known about the mechanisms of tissue damage involved in the gastrointestinal form, which was studied here. Chronically infected patients with a severe gastrointestinal form of Chagas' disease present increased antibody production and proliferative responses to peripheral myelin components, such as myelin basic protein (MBP), which is homologous to the P1 protein fraction of peripheral myelin. T lymphocytes preferentially recognize a region on the MBP molecule (1-30), which suggests that the MBP is a potential target on the peripheral nerve for autoimmune reactions in patients with gastrointestinal lesions resulting from Chagas' disease.
Subject(s)
Chagas Disease/immunology , Enteric Nervous System/immunology , Gastrointestinal Diseases/immunology , Myelin Sheath/immunology , Adult , Animals , Autoantibodies/immunology , Autoantigens/immunology , Autoimmunity/immunology , Brain/immunology , Brain/pathology , Brain/physiopathology , Chagas Disease/physiopathology , Enteric Nervous System/pathology , Enteric Nervous System/physiopathology , Female , Gastrointestinal Diseases/microbiology , Gastrointestinal Diseases/physiopathology , Gastrointestinal Tract/immunology , Gastrointestinal Tract/innervation , Gastrointestinal Tract/physiopathology , Humans , Lymphocyte Activation/immunology , Male , Middle Aged , Myelin Basic Protein/immunology , Myelin Proteins/immunology , Myelin Sheath/pathology , Neurons/immunology , Neurons/pathology , Peripheral Nerves/immunology , Peripheral Nerves/pathology , Peripheral Nerves/physiopathology , Polyradiculoneuropathy/immunology , Polyradiculoneuropathy/microbiology , Polyradiculoneuropathy/physiopathology , T-Lymphocytes/immunology , Trypanosoma cruzi/physiologySubject(s)
Antineoplastic Agents/therapeutic use , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cells/cytology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Thiazoles/therapeutic use , Adult , Benzamides , Dasatinib , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Male , Polymerase Chain Reaction , Remission InductionABSTRACT
Multiple sclerosis (MS) is a chronic inflammatory disease of the white matter of the central nervous system (CNS) characterized by focal areas of demyelination. Interferon-beta (IFN-beta) provides an effective treatment that lessens the frequency and severity of exacerbations in relapsing-remitting multiple sclerosis (RRMS), but the mechanisms by which IFN-beta is efficient remain uncertain. The data presented here demonstrate that IFN-beta impairs the proliferative response to myelin basic protein (MBP) and myelin, as well as increasing the expression of the CTLA4 intracellular molecule. Moreover, this treatment increases the expression of surface Fas molecules and of the soluble form of these molecules. Our hypothesis is that the increase in Fas and CTLA4 molecules in MS patients may lead to lymphocyte apoptosis, which suggests possible mechanisms underlying the therapeutic response to IFN-beta.
Subject(s)
Antigens, CD/metabolism , Antigens, Differentiation/metabolism , Interferon-beta/therapeutic use , Lymphocyte Activation/immunology , Multiple Sclerosis/drug therapy , Myelin Sheath/immunology , T-Lymphocytes/immunology , fas Receptor/metabolism , Adult , CD4-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/drug effects , CTLA-4 Antigen , Cell Proliferation/drug effects , Female , Humans , Interferon-beta/pharmacology , Lymphocyte Activation/drug effects , Male , Multiple Sclerosis/pathology , Myelin Basic Protein/metabolism , Myelin Sheath/drug effects , Solubility/drug effects , T-Lymphocytes/cytology , T-Lymphocytes/drug effects , fas Receptor/bloodABSTRACT
Interferon-beta (IFN-beta) is of benefit in the treatment of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), but the mechanisms by which it exerts this beneficial effect remain uncertain. The present data demonstrate that IFN-beta therapy impairs the proliferative response to concanavalin A (ConA) and myelin basic protein (MBP), decreases expression of the CD80 molecule on leukocytes of treated mice, and may thereby impede the Th1 cell activation-promoting anergy in EAE. Moreover, IFN-beta therapy increases expression of the CTLA4 molecule, which induces a counterregulatory Th2 response. The reduction of CD80 expression with concomitant increase of CTLA4 expression alters the course of EAE and may be useful as a monitor in therapy with IFN-beta.
Subject(s)
Encephalomyelitis, Autoimmune, Experimental/therapy , Interferon-beta/therapeutic use , Lymphocyte Activation/drug effects , T-Lymphocytes/drug effects , Animals , Antigens, CD , Antigens, Differentiation/metabolism , B7-1 Antigen/metabolism , CTLA-4 Antigen , Encephalomyelitis, Autoimmune, Experimental/immunology , Female , Interferon-beta/pharmacology , Mice , Multiple Sclerosis/immunology , Multiple Sclerosis/therapy , T-Lymphocytes/immunologyABSTRACT
This is the second of a two-part series looking at the increasing use of peripheral blood stem cell transplant as a treatment for certain types of malignancy. Last week's article reviewed the history of the treatment and discussed how the cells are collected. This article discusses the nursing care of patients undergoing transplant and looks at the future implications of the treatment.
Subject(s)
Hematopoietic Stem Cell Transplantation/nursing , Blood , Education, Nursing , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Humans , Patient Care PlanningABSTRACT
This is the first of a two-part article examining the increasing use of peripheral blood stem cell transplant as a treatment for certain types of malignancy. In this article the author reviews the history of the treatment and discusses how the cells are collected. The second article considers the nursing care of patients undergoing transplant and looks at the future implications of the treatment.
