Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats

Experimental autoimmune encephalomyelitis (EAE) is mediated by CD4+ Th1 cells that mainly secrete IFN-γ and TNF-α, important cytokines in the pathophysiology of the disease. Spontaneous remission is, in part, attributed to the down regulation of IFN-γ and TNF-α by TGF-β. In the current paper, we compared weight, histopathology and immunological parameters during the acute and recovery phases of EAE to establish the best biomarker for clinical remission. Female Lewis rats were immunised with myelin basic protein (MBP) emulsified with complete Freund's adjuvant. Animals were evaluated daily for clinical score and weight prior to euthanisation. All immunised animals developed the expected characteristics of EAE during the acute phase, including significant weight loss and high clinical scores. Disease remission was associated with a significant reduction in clinical scores, although immunised rats did not regain their initial weight values. Brain inflammatory infiltrates were higher during the acute phase. During the remission phase, anti-myelin antibody levels increased, whereas TNF-α and IFN-γ production by lymph node cells cultured with MBP or concanavalin A, respectively, decreased. The most significant difference observed between the acute and recovery phases was in the induction of TNF-α levels in MBP-stimulated cultures. Therefore, the in vitro production of this cytokine could be used as a biomarker for EAE remission.

Vacina de DNA contra doenças infecciosas / DNA vaccines against infectious diseases

A imunização ativa é um importante aliado da medicina moderna para o controle de doenças infecciosas. Muitas doenças infecciosas já foram controladas ou mesmo erradicadas através do uso de vacinas. No entanto muitas ainda permanecem resistentesàs tentativas de controle. O desenvolvimento recente da Imunologia e da Biologia Molecular permitiu o desenvolvimento da vacina de DNA, a qual apresenta seqüências do material genético do agente infeccioso que codificam antígenos imunodominantes. Ao contrário das vacinas tradicionais, as vacinas de DNA têm a capacidade de gerar resposta celular e humoral. Discutiremos nesse artigo as vacinas de DNA que estão sendo desenvolvidas para algumas doenças infecciosas causadas por vírus, bactéria e parasitas e também algumas considerações sobre segurança para uso destas vacinas nos seres humanos.

Active immunization is an important ally of modern medicine for the control of infectious diseases. Many infectious diseases have already been either controlled or eradicated through the use of vaccines. However, there are many that remain resistant to attempts at controlling them. The recent progress in Molecular Immunology and Biology have led to the development of the DNA vaccination. It presents sequences of genetic material of the infected agent which codifies immuno-dominant antigens. Differently from traditional vaccines, DNA vaccines are able to generate humoral and cellular responses. In this article, I discuss DNA vaccines which are being developed against certain infectious diseases caused by virus, bacteria and parasites. I also consider safety aspects with regard to the use of these vaccines in human beings.

Resistance to experimental autoimmune encephalomyelitis development in Lewis rats from a conventional animal facility

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the brain and spinal cord that is mediated by CD4+ T lymphocytes specific to myelin components. In this study we compared development of EAE in Lewis rats from two colonies, one kept in pathogen-free conditions (CEMIB colony) and the other (Botucatu colony) kept in a conventional animal facility. Female Lewis rats were immunized with 100 µl of an emulsion containing 50 µg of myelin, associated with incomplete Freund's adjuvant plus Mycobacterium butyricum. Animals were daily evaluated for clinical score and weight. CEMIB colony presented high EAE incidence with clinical scores that varied from three to four along with significant weight losses. A variable disease incidence was observed in the Botucatu colony with clinical scores not higher than one and no weight loss. Immunological and histopathological characteristics were also compared after 20 days of immunization. Significant amounts of IFN-gamma, TNF-alpha and IL-10 were induced by myelin in cultures from CEMIB animals but not from the Botucatu colony. Significantly higher levels of anti-myelin IgG1 were detected in the CEMIB colony. Clear histopathological differences were also found. Cervical spinal cord sections from CEMIB animals showed typical perivascular inflammatory foci whereas samples from the Botucatu colony showed a scanty inflammatory infiltration. Helminths were found in animals from Botucatu colony but not, as expected, in the CEMIB pathogen-free animals. As the animals maintained in a conventional animal facility developed a very discrete clinical, and histopathological EAE in comparison to the rats kept in pathogen-free conditions, we believe that environmental factors such as intestinal parasites could underlie this resistance to EAE development, supporting the applicability of the hygiene hypothesis to EAE.