Coevolution of hosts and microorganisms: an analysis of the involvment of cytokines in host-parasite interactions

Parasites may employ particular strategies of eluding an immune response by taking advantage of those mechanisms that normally guarantee immunological self-tolerance. Much in the way as it occurs during the establishment of self-tolerance, live pathogens may induce clonal deletion, functional inactivation(anergy) and immunosupression. At this latter level, it appears that certain pathogens produce immunosupresive cytokine-like mediators or provoke like host the secrete cytokines that will compromise the anti-parasite immune response. It appears that immune responses that preferentially involve T helper l cells (secretors of interleukin-2-and interferon-y) tend to be protective, whereas T helper 2 cells (secretors of IL-4, IL5, IL-6, and IL-10), a population that antagonizes T helper cells, mediate disease susceptibility and are immunopathological reactions. Cytokines produced by T helper 2 cells mediate many symptoms of infection, including eosinophilia, mastocytosis, hyperimmunoglobulinemia, and elevated IgE levels. Administration of IL-2 and IFN-y has beneficial effects in many infections mediated by viruses, bacteria, and protozoa. The use of live vaccinia virus might be an avenue for the treatment of or vaccination against infection. We have found that a vaccinia virus expressing the gene for human IL-2, though attenuated, precipitates autoimmune disease in immunodeficient athymic mice. Thus, although T helper l cytokines may have desired immunostimulatory properties, they also may lead to unwarranted autoaggressive responses.

Presence of Circulating Levels of Interferon-g, Interleukin-10 and Tumor Necrosis Factor-a in Patients with Visceral Leishmaniasis

Experimental murine L. major infection is characterized by the expansion of distinct CD4+ T cell subsets. The Th1 response is related to production of IFN-g and resolution of infection, whereas Th-2 response with production of IL-4 and IL-10 and dissemination of infection. The objective of this study was to measure the circulating levels of IFN-g, IL-10 and TNF-a in patients with visceral leishmaniasis (VL) before, during and at the end of therapy and to examine the association between cytokine levels and activity of VL. Fifteen patients with VL were evaluated. The cytokine determinations were done by using the enzyme-linked immunoassay (ELISA) before, during and at the end of therapy. At baseline, we detected circulating levels of IFN-g in 13 of 15 patients (median = 60 pg/ml); IL-10 in 14 of 15 patients (median = 141.4 pg/ml); and TNF-a in 13 of 14 patients (median = 38.9 pg/ml). As patients improved, following antimonial therapy, circulating levels of IL-10 showed an exponential decay (y = 82.34 e–0,10367x, r = –0.659; p < 0.001). IFN-g was no longer detected after 7/14 days of therapy. On the other hand, circulating levels of TNF-a had a less pronounced decay with time on therapy, remaining detectable in most patients during the first seven days of therapy (y = 36.99-0.933x, r = –0.31; p = 0.05). Part of the expression of a successful response to therapy may, therefore, include reduction in secretion of inflammatory as well as suppressive cytokines. Since IL-10 and IFN-g are both detected prior to therapy, the recognized cellular immune depression seen in these patients may be due to biological predominance of IL-10 (type 2 cytokine), rather than lack of IFN-g (type 1 cytokine) production.

Expression and biological activity of two recombinant polypeptides related to subunit 1 of the interferon-a receptor

Abnormal production of interferon alpha (IFN-a) has been found in certain autoimmune diseases and can be also observed after prolonged therapy with IFN-a. IFN-a can contribute to the pathogenesis of allograft rejection in bone marrow transplants. Therefore, the development of IFN-a inhibitors as a soluble receptor protein may be valuable for the therapeutic control of these diseases. We have expressed two polypeptides encoding amino acids 93-260 (P1) and 261-410 (P2) of the extracellular domain of subunit 1 of the interferon-a receptor (IFNAR 1-EC) in E. coli. The activities of the recombinant polypeptides and of their respective antibodies were evaluated using antiproliferative and antiviral assays. Expression of P1 and P2 polypeptides was achieved by transformation of cloned plasmid pRSET A into E. coli BL21(DE3)pLysS and by IPTG induction. P1 and P2 were purified by serial sonication steps and by gel filtration chromatography with 8 M urea and refolded by dialysis. Under reducing SDS-PAGE conditions, the molecular weight of P1 and P2 was 22 and 17 kDa, respectively. Polyclonal anti-P1 and anti-P2 antibodies were produced in mice. P1 and P2 and their respective polyclonal antibodies were able to block the antiproliferative activity of 6.25 nM IFN-aB on Daudi cells, but did not block IFN-aB activity at higher concentrations (>6.25 nM). On the other hand, the polypeptides and their respective antibodies did not inhibit the antiviral activity of IFN-aB on Hep 2/c cells challenged with encephalomyocarditis virus.

Interferon-alpha receptor 1 mRNA expression in peripheral blood mononuclear cells is associated with response to interferon-alpha therapy of patients with chronic hepatitis C

Interferon (IFN)-alpha receptor mRNA expression in liver of patients with chronic hepatitis C has been shown to be a response to IFN-alpha therapy. The objective of the present study was to determine whether the expression of mRNA for subunit 1 of the IFN-alpha receptor (IFNAR1) in peripheral blood mononuclear cells (PBMC) is associated with the response to IFN-alpha in patients with chronic hepatitis C. Thirty patients with positive anti-HCV and HCV-RNA, and abnormal levels of alanine aminotransferase in serum were selected and treated with IFN-alpha2b for one year. Those with HBV or HIV infection, or using alcohol were not included. Thirteen discontinued the treatment and were not evaluated. The IFN-alpha response was monitored on the basis of alanine aminotransferase level and positivity for HCV-RNA in serum. IFNAR1-mRNA expression in PBMC was measured by reverse transcription-polymerase chain reaction before and during the first three months of therapy. The results are reported as IFNAR1-mRNA/ß-actin-mRNA ratio (mean ± SD). Before treatment, responder patients had significantly higher IFNAR1-mRNA expression in PBMC (0.67 ± 0.15; N = 5; P < 0.05) compared to non-responders (0.35 ± 0.17; N = 12) and controls (0.30 ± 0.16; N = 9). Moreover, IFNAR1-mRNA levels were significantly reduced after 3 months of treatment in responders, whereas there were no differences in IFNAR1 expression in non-responders during IFN-alpha therapy. Basal IFNAR1-mRNA expression was not correlated with the serum level of alanine and aspartate aminotransferases or the presence of cirrhosis. The present results suggest that IFNAR1-mRNA expression in PBMC is associated with IFN-alpha response to hepatitis C and may be useful for monitoring therapy in patients with chronic hepatitis C.

Entender a Rusia a través de sus fuerzas profundas: dificultades y desafíos de una reflexión recurrente

Este artículo analiza rasgos que por su persistencia en prolongados períodos históricos pueden ser considerados como elementos que contribuyen a moldear la identidad de la nación rusa. Estas "fuerzas profundas" son: el excepcionalismo, el mesianismo, el externalismo, el territorialismo y el peso del Estado. También se aborda a las "fuerzas organizadas" como actores estatales y burocracias. Se reflexiona sobre el peso y la vigencia de algunos de estas fuerzas en los debates sobre la política exterior contemporánea.

Argentina y Brasil en la Política Internacional: regionalismo y Mercosur (estrategias, cooperación y factores de tensión)

Este artículo analiza la política de Brasil y Argentina en relación a los procesos de integración y cooperación regionales, en particular hacia el Mercosur. Se hace previamente una reflexión teórica sobre la regionalización o regionalismo, luego se presenta someramente el Mercosur para en seguida abordar las respectivas políticas exteriores. En Sudamérica el Mercosur coexiste hoy con otras dos iniciativas. Como nuevos escenarios de regionalización aparecen, desde diciembre de 2004 la Unasur (Unión Sudamericana de Naciones) como esquema de cooperación y concertación liderado por Brasil y, desde la misma época, ALBA (Alternativa Bolivariana de Integración) promovida por el presidente Chávez como proyecto contrario al Mercosur, al cual considera "neoliberal".

La Argentina y el Plan Marshall: promesas y realidades

El artículo analiza los intereses y prioridades de la política económica externa de los Estados Unidos y las complejas relaciones entre Washington y el gobierno de Buenos Aires en relación a la puesta en marcha del Plan Marshall de reconstrucción de Europa Occidental. La no participación de la Argentina en él dificultó su proceso de industrialización al restringir su comercio con el viejo continente e impedirle obtener las divisas necesarias para comprar en los EEUU, proveedor fundamental de los bienes que necesitaba.

América Latina a inicios de la segunda década del siglo XXI: entre el regionalismo estratégico y la regionalización fragmentada

El artículo analiza la evolución del regionalismo en América Latina desde los años noventa. Expone las opciones que se plantean a los países en sus políticas exteriores frente a las iniciativas de Estados Unidos y los cambios en el sistema internacional. Se expone la importancia funcional de las potencias emergentes (PEMS) y las regiones en la fase actual del capitalismo. Finalmente el artículo analiza las perspectivas del regionalismo en América Latina tanto en el sistema internacional como en la construcción de un modelo de gobernanza regional.

Los desafíos a la reunificación de China y Taiwán: la Ley Antisecesión (2005) y el Acuerdo Marco de Cooperación Económica (2010)

El presente artículo tiene por objetivo analizar el problema de la reunificación entre la República Popular China y Taiwán en la última década, en el marco de dos hitos: por un lado, la promulgación de la Ley Antisecesión del 14 de marzo de 2005 y, por otro, la firma del Acuerdo Marco de Cooperación Económica el 30 de junio de 2010.