Two immunomodulators, curcumin and sulfasalazine, enhance IDV antiretroviral activity in HIV-1 persistently infected cells.

Since the appearance of resistance to antiretroviral treatment is unavoidable, the host cell's transcription factor NF-kappaB is a novel HIV target. The goal of this study was to characterize the effect of two immunomodulators, curcumin (Cur) and sulfasalazine (Sul), with a protease inhibitor, indinavir (IDV), on HIV-1 persistently infected CD4+ T-cells. Viral p24 antigen production, viral infectivity (tested on MAGI cells) and viral relative infectivity (viral infectivity/p24) were analysed. When used alone, both immunomodulators were able to reduce viral infectivity. When in combination, both 10 microM IDV plus 10 microM Cur and 10 microM IDV plus 250 microM Sul showed a significant reduction in viral infectivity and viral relative infectivity when compared to the reduction produced by IDV alone. Thus, the use of immunomodulators with IDV could help to reduce HIV-1 production in persistently infected cells.

Virucidal activity presence in Trichilia glabra leaves.

Different immunomodulatory activities present in Trichilia glabra (TG) leaf extracts have already been described. Particularly, chloroform-methanol extracts were responsible for an in-vivo anti-inflammatory effect. The effect of such extracts on the infectivity of enveloped and naked viruses were investigated. Methanolic fraction extracts were active against herpes simplex virus type 1 (HSV-1) and vesicular stomatitis virus (VSV), while no activity against poliovirus type 3 was observed. VSV was slightly more affected than HSV-1: 2.8 log10 reduction in VSV titer against 2.4 log10 reduction in HSV-1 titer when 0.25 mg/ml F2 fraction was tested and a reduction of 2.7 log10 in VSV virus titer and of 1.5 log10 in HSV-1 virus titer was observed when 0.25 mg/ml F3 fraction was tested. Results obtained in this work suggest a potential pharmaceutical use of TG extract components.

Virucidal activity presence in Trichilia glabra leaves / Presencia de actividad antiviral en hojas de Trichilia glabra

Different immunomodulatory activities present in Trichilia glabra (TG) leaf extracts have already been described. Particularly, chloroform-methanol extracts were responsible for an in-vivo anti-inflammatory effect. The effect of such extracts on the infectivity of enveloped and naked viruses were investigated. Methanolic fraction extracts were active against herpes simplex virus type 1 (HSV-1) and vesicular stomatitis virus (VSV), while no activity against poliovirus type 3 was observed. VSV was slightly more affected than HSV-1: 2.8 log10 reduction in VSV titer against 2.4 log10reduction in HSV-1 titer when 0.25 mg/ml F2 fraction was tested and a reduction of 2.7 log10in VSV virus titer and of 1.5 log10in HSV-1 virus titer was observed when 0.25 mg/ml F3 fraction was tested. Results obtained in this work suggest a potential pharmaceutical use of TG extract components.

Previamente se han descripto distintas actividades inmunomoduladoras, presentes en extractos de hojas de Trichilia glabra (TG). En particular, se ha demostrado una actividad antiinflamatoria presente en extractos metanólicos. En este trabajo se investigó la actividad virucida de dichos extractos sobre virus envueltos y desnudos. Distintos extractos metanólicos han inactivado en forma moderada los virus herpes simplex tipo 1 (HSV-1) y el virus de la estomatitis vesicular (VSV), mientras no evidenciaron actividad sobre poliovirus tipo 3. VSV resultó algo mas afectado que HSV-1: se observó una reducción en el título viral de 2,8 log10para VSV y de 2,4 log10para HSV-1 cuando se uso una concentración de 0,25 mg/ml de la fracción F2 y una reducción de 2,7 log10para VSV y de 1,5 log 10para HSV-1 cuando se usó una concentración de 0,25 mg/ml de la fracción F3. Los resultados obtenidos en este trabajo, sugieren un potencial uso farmacéutico de los componentes presentes en los extractos de TG.

Virucidal activity presence in Trichilia glabra leaves.

Different immunomodulatory activities present in Trichilia glabra (TG) leaf extracts have already been described. Particularly, chloroform-methanol extracts were responsible for an in-vivo anti-inflammatory effect. The effect of such extracts on the infectivity of enveloped and naked viruses were investigated. Methanolic fraction extracts were active against herpes simplex virus type 1 (HSV-1) and vesicular stomatitis virus (VSV), while no activity against poliovirus type 3 was observed. VSV was slightly more affected than HSV-1: 2.8 log10 reduction in VSV titer against 2.4 log10 reduction in HSV-1 titer when 0.25 mg/ml F2 fraction was tested and a reduction of 2.7 log10 in VSV virus titer and of 1.5 log10 in HSV-1 virus titer was observed when 0.25 mg/ml F3 fraction was tested. Results obtained in this work suggest a potential pharmaceutical use of TG extract components.

Antiviral activity of an acidic polysaccharides fraction extracted from Cedrela tubiflora leaves.

An acidic polysaccharides fraction (APS) obtained from Cedrela tubiflora leaves was tested for antiviral activity. This fraction inhibited the replication of HSV-2 and VSV, while the replication of poliovirus was not affected. APS was not virucidal, but no cytotoxicity was present in the different concentrations of APS assayed.

Anti-inflammatory activities of Trichilia glabra aqueous leaf extract.

Trichilia glabra L. aqueous leaf extract exerted a significant antiinflammatory effect 'in vivo' in the zymosan-induced inflammation model. The extract impaired the 'in vitro' activities of polymorphonuclear leukocytes and complement, components of mouse immune system closely related to the inflammatory response induced by zymosan. In particular, a significant reduction in the phagocytic capability and respiratory burst response of mouse polymorphonuclear leukocytes together with an inhibition in the hemolytic activity of mouse complement was observed.

In vivo and in vitro immunomodulatory activities of Trichilia glabra aqueous leaf extracts.

The effects of Trichilia glabra (Meliaceae) aqueous leaf extract on mouse lymphocytes were studied. The in vitro proliferation of T and B lymphocytes was completely impaired. Besides, the extract significantly diminished both antibody and delayed hypersensitivity responses in treated mice. These results suggest that the extract exerts a marked immunomodulatory effect on the murine immune system.

Trichilia glabra: effect on the phagocytic activity and respiratory burst response of peritoneal macrophages.

A diminution in the phagocytic capability and respiratory burst response of murine peritoneal macrophages was observed when these cells were treated 'in vitro' with Trichilia glabra leaf aqueous extract. The effect was not observed when non-specific phagocytosis was tested. The extract also inhibited binding of opsonized erythrocytes to macrophages, thus indicating that the observed antiphagocytic effect is possibly due to the failure of opsonized particles to bind to these cells. A low molecular weight fraction is responsible for the reported activities.

Neutral polysaccharide from Cedrela tubiflora with anticomplementary activity.

A water-soluble polysaccharide extracted from leaves of the Meliaceae Cedrela tubiflora was separated into neutral and acidic polysaccharide fractions. The best anticomplementary activity was exhibited by the neutral product which was further purified by means of gelpermeation chromatography. The composition and methylation analysis of the purified product were determined.

In vitro and in vivo activities of Melia azedarach L. aqueous leaf extracts on murine lymphocytes.

The effect of Melia azedarach L. aqueous leaf extracts (Ma) on in vitro lymphocyte proliferation and humoral and cellular immune responses in vivo was studied. Proliferation of spleen and lymph node T cells was impaired when these cells were incubated in the presence of the extract using different mitogens as stimuli. Furthermore, treatment of mice with the extracts not only diminished the production of antibodies but also exerted an inhibition on graft vs host and delayed type hypersensitivity reactions. These results suggest that Ma extracts exert a marked immunomodulatory effect on the mouse immune system.

Immunomodulatory activities of Cedrela lilloi and Trichilia elegans aqueous leaf extracts.

The effects of Cedrela lilloi and Trichilia elegans (Meliaceae) aqueous leaf extracts on several parameters of the mouse immune system were studied. Both extracts showed a strong anticomplementary activity and inhibited the phagocytosis of opsonized sheep erythrocytes and the activation of the oxidative metabolism by opsonized zymosan on peritoneal macrophages. The in vitro proliferation of spleen T-lymphocytes was also impaired. Furthermore, treatment of mice with the extracts diminished the delayed-type hypersensitivity response to sheep erythrocytes. These results suggest that both extracts exert a marked immunomodulatory effect on the mouse immune system.

Immunomodulatory activities of Cedrela tubiflora leaf aqueous extracts.

Human peripheral blood monocytes and polymorphonuclear leukocytes treated with leaf aqueous extracts of the Meliaceae tree Cedrela tubiflora showed a diminution in both their phagocytic and respiratory burst activities. Besides, the extract inhibited the proliferation of Concanavalin A stimulated lymphocytes. A decrease in the hemolytic capacity of the human complement was also observed. The significance of the inhibitory effect observed over some components of the human immune system closely related with the inflammatory process is discussed.

In vitro antiphagocytic effect of Melia azedarach leaf extracts on mouse peritoneal exudate cells.

The effect of Melia azedarach L. (Meliaceae) leaf extract on the phagocytic capability and respiratory burst of mouse peritoneal exudate cells was studied. The extract inhibited the phagocytosis of opsonized sheep erythrocytes. This inhibition was both dose- and time-dependent and reverted 48 h after removing the extract from the culture medium. Furthermore, chemiluminescence in treated cells was also impaired using either receptor (opsonized zymosan) or post-receptor (PMA) stimuli.

Effect of Melia azedarach L. leaf extracts on human complement and polymorphonuclear leukocytes.

The effect of the water extract of Melia azedarach L. (Meliaceae) leaves on human complement and polymorphonuclear leukocytes was investigated. This extract showed a strong anticomplementary activity, which was more pronounced in the classical pathway assay. The extract did not affect the phagocytic activity of polymorphonuclear leukocytes, nor the respiratory burst of these cells as measured by the nitro blue tetrazolium reduction assay.

Meliacine, an antiviral compound from Melia azedarach L., inhibits interferon production.

A glycopeptide isolated from the high plant Melia azedarach L. (meliacine) inhibits the in vitro replication of several RNA and DNA animal viruses. Interferon (IFN) production was depressed greatly in meliacine treated L929 cells and primary mouse embryo fibroblast cultures (MEF) induced with Newcastle disease virus (NDV) or poly(rI).poly(rC). This action was observed when meliacine was added before, simultaneously or early after induction with poly(rI).poly(rC) or NDV. In addition, accumulation of acid-resistant IFN was strongly diminished in adult mice treated intraperitoneally with meliacine. Though meliacine causes a strong inhibition of IFN both in vitro and in vivo, we do not know how selectively it affects the IFN system.

Role of Calomys musculinus peritoneal macrophages in age-related resistance to Junin virus infection.

In nature, the cricetid Calomys musculinus is the principal host of Junin virus, the etiological agent of Argentine hemorrhagic fever. In the experimental infection, adult C. musculinus survived whereas newborns died after intraperitoneal inoculation with the XJ.Cl3 strain of Junin virus. The role of peritoneal macrophages in this age-related resistance was studied. Junin virus multiplied in cultivated macrophages from either neonatal or adult animals and, therefore, it was not possible to correlate the susceptibility of peritoneal macrophages to Junin virus infection with the age-dependent resistance. When adult and neonatal animals were treated with silica prior to Junin virus infection, deaths occurred in the adults, while a delay and decrease in the mortality rate were observed in neonatals. These results suggest that in neonatal C. musculinus macrophages could be permissive cells for Junin virus multiplication, whereas in adult cricetids, these cells would act as a barrier against viral infection by means of an extrinsic antiviral activity.

Administration of antithymocyte serum modifies the response of Calomys musculinus to junin virus infection.

Approximately 80% of Calomys musculinus inoculated with an attenuated strain of Junin virus (JV) developed a lethal encephalitis. Antithymocyte serum, a potent suppressor of T-cell-mediated immunity, was studied for its effect on JV pathogenicity. Early administration of an anti-C. musculinus thymocyte serum (ACTS) to neonatal animals significantly diminished clinical disease and death and abrogated brain damage, which is usually associated with viral presence in the brain. Late ACTS administration did not modify the pattern of JV infection. These results suggest that immune mechanisms participate in the pathogenesis of JV infection for its main natural host.

[Isolation of Junin virus from blood and peripheral lymphocytes of infected Calomys musculinus]. / Aislamiento de virus Junín a partir de sangre y linfo-monocitos periféricos de Calomys musculinus infectados.

Neonatal Calomys musculinus experimental infection with Junín virus (JV) XJCl3 strain causes either death or a persistent infection in the major part of surviving animals. JV can be isolated from peritoneal macrophages early during infection, and from brain and salivary glands during the chronic state of disease. It was of interest to investigate the appearance of virus in blood of infected animals. For this purpose, we decided to study the development of viremia in inoculated cricetids. A high frequency of viremia was registered during the acute state of disease (figure 1), which became sporadic approximately from 20 days post-infection onwards. Considering the results above mentioned, the characteristic lymphotropism of arenaviruses and the well-known JV replication in human mononuclear cells, cultures of lympho-monocytes obtained from blood of infected C. musculinus were done in order to investigate the eventual detection of infectious virus in the supernatants. JV was isolated, although in low titres, from cultures established with mononuclear cells belonging to animals in the acute state of disease (table 1); in the case of chronically infected cricetids, attempts to isolate JV were negative. These results show that viremia is currently detected in experimentally infected C. musculinus and that circulating mononuclear cells are permissive for JV multiplication, during the acute state of disease.