The use of interferons in the treatment of pre-invasive cervical neoplasias

The evolution of cervical intraepithelial neoplasias(CINs) can lead to the development of cervical carcinomas and is closely tied to infection with human papillomavirus (HPV). Interferon (IFN)’s antitumor effects have a direct bearing on the proliferation or antigen composition of tumor cells, and act on specific tumor cells through immunomodulation. Moreover, some studies have indicated that type 1 IFN can have an antitumor effect by increasing levels of cytotoxic T cells,natural killer (NK) cells and dendritic cells (DCs). Immunotherapy with IFN has recently been used on cervical intraepithelial lesions and invasive cervical cancer with promising results. The objective of this mini-review isto discuss IFNs’ function, importance, and mechanism of action in the treatment of pre-malignant cervicalneoplasias.

Interferón: 50 años después (1957-2007) / A review of interferons: fifty years later (1957-2007)

Identificados inicialmente como un mecanismo de defensa contra las infecciones virales, en el transcurso de los últimos 50 años se ha definido que los interferones forman parte de la extensa familia de las citocinas, sustancias indispensables para el funcionamiento del sistema inmunológico. Debido a sus diversas funciones pleiotrópicas, los interferones fueron las primeras citocinas empleadas para el manejo de una amplia gama de padecimientos, propiedades que progresivamente los han colocado como medicamentos de primera elección para el tratamiento de la infección crónica por el virus de la hepatitis B, virus de la hepatitis C, esclerosis múltiple, algunas leucemias, melanoma, etc. No obstante, la administración de dosis suprafisiológicas de interferones con fines terapéuticos, independientemente de su indicación primaria, se han asociado con toxicidad importante, incluyendo la inducción de autoinmunidad y más de 30 enfermedades autoinmunes diferentes.

Initially identified as a defense mechanism against viral infections, in the last 50 years interferons have been defined a group of substances belonging to the cytokine family indispensable for the normal functioning of the immune system. Derived from their pleiotropic functions interferons were the first biological products used to treat several diseases. Their properties have progressively placed them as the first treatment choice for chronic infection with hepatitis B virus, hepatitis C virus, multiple sclerosis, some forms of leukemia, melanoma, etc. It has been noted however that the administration of supra physiological doses of interferons with therapeutic objectives, independently of its primary indication, has been associated with significant toxicity, including autoimmunity and induction of more than thirty different autoimmune diseases.

Efectos contrapuestos de interleuquina-2 (IL-2) e interferón-y (IFN-y) sobre contractilidad cardíaca / Opposed efects of interleukin 2 (IL-2) and interferon-y (IFN-y) on cardiac contractility

Recientemente demostramos que la interleuquina 2 (IL-2) es capaz de incrementar la tensión contráctil de aurículas de rata asiladas a través de la activación de las fosfolipasas y de la proteína quinasa C. Los resultados de este estudio demuestran que la vía ß-adrenérgica está involucrada en la acción de IL-2 sobre el miocardio mientras que el IFNy interactúa con los colinoceptores muscarínicos. El efecto estimulante de IL-2 sobre la contractilidad se opone al efecto colinomimético inhibitorio del interferón y (IFNy). La preincubación de las aurículas con IL-2 suprime la respuesta al IFNy y viceversa. La proteína quinasa C es también necesaria para que ocurra la interferencia IL-2-IFNy. Los resultados de este estudio sugieren que, durante un proceso inflamatorio en el corazón, el balance local de ambas linfoquinas puede determinar cambios en la respuesta del tejido hacia agonistas propios del sistema nervioso autónomo y hacia las citoquinas que imitan los efectos de dichos neurotransmisores.

IRF-1 and IRF-2 as regulators of the interferon system and cell growth.

Interferons (IFNs) are families of cytokines which have been discovered and extensively characterized in the context of host defense against viral infections. We have discovered two structurally related transcription factors, Interferon regulatory factor-1 (IRF-1) and IRF-2. These two factors, however, function not only as regulators of the IFN system, but are also key transcription factors in the regulation of cell cycle and apoptosis. These studies uncover a complex gene transcription network, by which the fate of cellular responses are determined depending on how the IRF transcription factors function in conjunction with other factors, and on the promoters of distinct genes under different conditions of the cells.

Oncogene.

Recent studies have shown that activation of oncogenes, genes concerned with cell growth, and inactivation of anti-oncogenes may be responsible for uncontrolled cell proliferation leading to malignancy. These oncogenes code for products or proteins which are closely similar to growth factors or receptors of growth factors. Alterations in lipid metabolism in the form of excess formation of inositol triphosphate and relocation of protein kinase C, the second messengers of the mitotic process, can initiate cell division. Oncogenes can be activated by chromosomal aberrations induced by chemicals, viruses and drugs. The identification of oncogenes and their products may have relevance to the development of new therapeutic strategies in cancer.

Hematopoese: I. Citocinas envolvidas em sua regulaçäo / Hematopoiesis: I. Cytokines involved in its regulation

O estudo da participaçäo direta de citocinas, tais como os fatores estimuladores do crescimento de colônias, as interleucinas, e outros, no controle das etapas da hematopoese, vem sendo prejudicado pela presença in vitro de células näo-hematopoéticas, capazes de intermediar os efeitos das citocinas sobre os precursores hematopoéticos. Recentemente pôde-se verificar que o antígeno CD34 se expressa na membrana de essencialmente todas as células pluripotenciais, mas näo da maioria das células diferenciadas do sangue ou do estroma da medula óssea, o que veios a permitir experimentos in vitro com populaçöes ricas em células pluripotenciais, purificadas com base na expressäo deste antígeno. Tais experimentos permitiram uma reavaliaçäo dos resultados obtidos previamente com populaçöes menos puras e ampliaram o conhecimento sobre a participaçäo das diferentes citocinas nos processos de diferenciaçäo das distintas linhagens hematopoéticas, tema desta revisäo. O papel de interferons, fatores necrosantes de tumor e fatores de transformaçäo de crescimento ß na regulaçäo negativa da hematopoese säo também analisados