Preparation of apoptotic tumor cells with replication-incompetent HSV augments the efficacy of dendritic cell vaccines.

The use of dendritic cells (DCs) loaded with apoptotic tumor cells is an attractive approach to tumor vaccination in the absence of well-characterized tumor antigens. Apoptotic tumor cells are a convenient source of polyvalent tumor antigen, but may induce only weak immunization. We tested the role of replication-incompetent recombinant herpes simplex virus (HSV) d106 lacking all immediate early genes except ICP0 in the generation of apoptotic cells for tumor vaccination, using ID8-VEGF, a syngeneic mouse model of ovarian carcinoma expressing high levels of VEGF, and TC-1, a human papillomavirus (HPV) 16 E6- and E7-transformed adenocarcinoma. HSVd106 killed tumor cells by apoptosis. Tumor cells infected by HSVd106 were engulfed more avidly by immature DCs, and induced DC maturation more efficiently than tumor cells killed by ultraviolet B (UVB) radiation. HSVd106 infection induced stronger upregulation of heat shock protein (Hsp) 70 and glucose-related protein (GRP) 94 than UVB in cells undergoing apoptosis. Immunization of mice with DCs loaded with HSVd106-killed cells elicited stronger antitumor T-cell response, including tumor-reactive interferon-gamma-secreting and cytotoxic T cells, and resulted in significantly stronger delay in tumor growth than immunization with DCs loaded with UVB-killed tumor cells. Moreover, in the TC-1 model, a protective effect of vaccination (40% tumor free animals) was observed only after immunization with DCs loaded with HSVd106-killed cells. Thus, the use of replication-incompetent HSV strains lacking immediate early genes except ICP0 offers possible advantages in the preparation of whole tumor cell antigen for DC-based tumor vaccination.

In vitro antiphagocytic effect of basil oil on mouse macrophages.

The effect of basil oil on the phagocytic capability and respiratory burst response of mouse peritoneal macrophages was studied. The oil inhibited the phagocytosis of opsonized sheep erythrocytes. This inhibition was both dose- and time-dependent and reverted 24 h after removing the extract from the culture medium. On the other hand, the oil showed no effect on concanavalin A and lipopolysaccharide-induced proliferation.

Effect of aminoguanidine, a nitric oxide synthase inhibitor, on ocular infection with herpes simplex virus in Balb/c mice.

PURPOSE: To study the effect of aminoguanidine (AMG), an inhibitor of nitric oxide production, on the ocular infection of Balb/c mice with herpes simplex virus (HSV) type 1 strain F and HSV-2 strain G. METHODS: Animals were treated with different amounts of AMG (0.5, 0.1, and 0.05 mg/mouse) by topical application in the eye from postinfection (PI) days -2 through +5, considering 0 the day of infection. At different PI days, development of herpetic keratitis was evaluated in treated and control mice. RESULTS: Treated animals showed a dose-dependent increase in ocular disease after viral infection, compared with control animals. Viral titers in ocular washings were higher in AMG-treated mice (PI day 2, HSV-1: AMG 0.5 mg, 1.3 x 10(3) plaque-forming units (PFU)/ml; control, 0. 22 x 10(2) PFU/ml, P < 0.025). At PI day 3, control corneas had only scattered inflammatory cells, whereas those from treated animals showed a conspicuous infiltrate consisting primarily of neutrophils. Viral titers were also higher in brains of treated mice. These animals died earlier and in a greater proportion than control animals (percentage of mortality, PI day 12, HSV-1: AMG 0.5 mg, 40% +/- 4%; control, 18% +/- 3%, P < 0.05). CONCLUSIONS: These data indicate an inhibitory effect of nitric oxide on HSV ocular infection.

In vitro and in vivo activity of eugenol on human herpesvirus.

Eugenol (4-allyl-1-hydroxy-2-methoxybenzene) was tested for antiviral activity against HSV-1 and HSV-2 viruses. In vitro, it was found that the replication of these viruses was inhibited in the presence of this compound. Inhibitory concentration 50% values for the anti-HSV effects of eugenol were 25.6 microg/mL and 16.2 microg/mL for HSV-1 and HSV-2 respectively, 250 microg/mL being the maximum dose at which cytotoxicity was tested. Eugenol was virucidal and showed no cytotoxicity at the concentrations tested. Eugenol-acyclovir combinations synergistically inhibited herpesvirus replication in vitro. Topical application of eugenol delayed the development of herpesvirus induced keratitis in the mouse model.

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.

Nitric oxide and macrophage antiviral extrinsic activity.

In this study we evaluated the relationship between nitric oxide (NO) and macrophage antiviral extrinsic activity. Macrophages activated by intraperitoneal injection of herpes simplex virus-2 (HSV-2), showed both extrinsic antiviral activity and high nitrite production in contrast to non-activated, resident macrophages. The extrinsic antiviral activity was observed in cultures of Vero cells infected with HSV-1 and HSV-2. The NO inhibitor N-monomethyl-l-arginine acetate (l-NMA) impaired the antiviral activity of HSV-elicited macrophages. The effect was dose dependent and correlated with a reduction of nitrite in the culture media. The effect of l-NMA was reversed by the addition of l-arginine. These data indicate that NO could be responsible for the described activity. Furthermore, l-NMA treatment resulted in the aggravation of HSV-1-induced keratitis in the mouse model, supporting a defensive role of NO in the pathogenesis of HSV-1 corneal infection.

Antiviral activity of sandalwood oil against herpes simplex viruses-1 and -2.

Sandalwood oil, the essential oil of Santalum album L., was tested for in vitro antiviral activity against Herpes simplex viruses-1 and -2. It was found that the replication of these viruses was inhibited in the presence of the oil. This effect was dose-dependent and more pronounced against HSV-1. A slight diminution of the effect was observed at higher multiplicity of infections. The oil was not virucidal and showed no cytotoxicity at the concentrations tested.

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.

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.