ABSTRACT
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
O conhecimento a respeito das características e do comportamento da doença de Hodgkin, no Brasil, näo está completamente estabelecido e há poucos estudos descritos na literatura internacional sobre a nossa realidade. O autor estudou 134 casos da doença de Hodgkin acima de 15 anos de idade, retrospectiva e exploratoriamente, envolvendo 76 do sexo masculino e 58 do feminino, de 1985 a 1994, atendidos em um único hospital universitário de referência, para uma regiäo de 6 milhöes de habitantes. Foram estudados os dados clínicos, laboratoriais, radiológicos, tomográficos, ultra-sonográficos, histopatológicos e evolutivos em todos os pacientes, ao diagnóstico e após o tratamento protocolar da istituiçäo. A doença de Hodgkin apresentou predomínio no sexo masculino (R=1,31); pico de incidência entre 21 e 30 anos; 2/3 dos casos abaixo dos 40 anos; e curva decrescente de incidência após os 30 anos. O tipo histológico mais freqüente foi a esclerose nodular (50,4 por cento), seguido pelos de celularidade mistra (34,6 por cento), depleçäo linfocitária (9 por cento) e predominância linfocitária (5,2 por cento). O tipo esclerose nodular-I prevaleceu sobre o tipo esclerose nodular-II (30,8 por cento e 19,6 por cento respectivamente). O tipo esclerose nodular foi singnificativamente mais freqüente nas mulheres e o tipo celularidade mista, nos homens...
