Presente y futuro de la terapia inmunosupresora / [Present and future of immunosuppressive therapy]

Immunosuppressive drugs make possible the acceptance of organ allografts among individuals with differences in Major Histocompatibility Antigens (HLA). Transplantation of vital organs prolongs the survival of patients with terminal diseases, and this procedure has become a routine practice in the clinic, mainly because of advances in immunosuppressive therapy. Some immunosuppressive drugs, such as glucocorticosteroids and azathioprine, have been used for the past 30 years. More recently, newly discovered agents with a better ratio of efficacy to toxicity have been added to the armamentarium of anti-rejection therapies. Progress in understanding T cell activation in response to alloantigens has contributed to the development of new and more selective strategies to control the immune response and prevent acute rejection. The use of drugs in combination, with or without monoclonal antibodies, has also improved the efficacy and reduced the toxicity of immunosuppressive therapies. The new agents include drugs that interfere with calcineurin, inhibitors of de novo purine biosynthesis, kinase inhibitors, as well as monoclonal antibodies that block activation signals on the surface of T cells or co-stimulatory signals between T cells and antigen-presenting cells. In this review the modes of action of commonly used immunosuppressive drugs are described. Successful new strategies are also being developed to establish tolerance to allografts in rodents and non-human primates. The progress in these approaches, although still in the experimental stages, offers promising alternatives for these patients in the future. Treatment protocols using combinations of drugs with antibodies that might produce tolerance in humans are also discussed.

Evaluacion de linfocitos perifericos en pacientes con tumores solidos malignos. / Evaluation of peripheral lymphocytes in patients with solid malignant tumors

Mediante la identificacion de diferentes poblaciones de linfocitos perifericos, se realizo un estudio comparativo entre 32 pacientes con neoplasias solidas malignas de distinto origen, sin tratamiento oncologico previo y 17 controles sanos. Para su evaluacion se utilizaron las tecnicas de formacion de rosetas espontaneas con globulos rojos de carnero (rosetas E) para linfocitos T, de rosetas EAC para celulas con receptor para el complemento, y de inmunofluorescencia directa para linfocitos con Ig de superficie. Ademas, se valoro el numero total de leococitos y el porcentaje de linfocitos antes y despues del tratamiento antineoplasico instituido. Los valores correspondientes al % de rosetas E, no mostraron diferencias entre los distintos grupos de enfermos ni con relacion a los controles normales. Con respecto al % de rosetas EAC no se observaron diferencias entre los testigos y los distintos grupos de enfermos estudiados, aunque si pudieran advertirse entre los pacientes con adenocarcinomas y los portadores de melanomas (p < 0.05). Los resultados obtenidos en el estudio de celulas con Ig de superficie, mostraron diferencias entre los enfermos con adenocarcinomas y los testigos sanos, y con el grupo de Ca epidermoide. El % de linfocitos antes y despues del tratamiento, fue similar en los enfermos con melanomas, adenocarcinomas y carcinomas epidermoides, pero disminuyo sensiblemente en el grupo con cancer de pulmon, estimandose que ese porcentaje durante la enfermedad, estaba en relacion directa con el periodo de sobrevida de los pacientes