RESUMO
Acne, also known as acne vulgaris, is a common disorder of human skin involving the sebaceous gland and Propionibacterium acnes (P. acnes). Although there are a number of treatments suggested for acne, many of them have limitations in their safety and have efficacy issues. Therefore, there is a high demand to develop safe and effective novel acne treatments. In the present study, we demonstrate the protective effects of Rosa davurica Pall. leaves (RDL) extract against P. acnes-induced inflammatory responses in vitro and in vivo. The results showed that RDL dose-dependently inhibited the growth of skin bacteria, including P. acnes (KCTC3314) and aerobic Staphylococcus aureus (KCTC1621) or Staphylococcus epidermidis (KCTC1917). The downregulation of proinflammatory cytokines by RDL appears to be mediated by blocking the phosphorylations of mitogen-activated protein kinase (MAPK) and subsequent nuclear factor-kappa B (NF-κB) pathways in P. acnes-stimulated HaCaT cells. In a mouse model of acne vulgaris, histopathological changes were examined in the P. acnes-induced mouse ear edema. The concomitant intradermal injection of RDL resulted in the reduction of ear swelling in mice along with microabscess but exerted no cytotoxic effects for skin cells. Instrumental analysis demonstrated there were seven major components in the RDL extract, and they seemed to have important roles in the anti-inflammatory and antimicrobial effects of RDL. Conclusively, our present work showed for the first time that RDL has anti-inflammatory and antimicrobial effects against P. acnes, suggesting RDL as a promising novel strategy for the treatment of acne, including natural additives in anti-acne cosmetics or pharmaceutical products.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Edema/imunologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/imunologia , Propionibacterium acnes/patogenicidade , Rosa/química , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Edema/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Propionibacterium acnes/imunologiaRESUMO
The microbiome represents a vast resource for drug discovery, as its members engage in constant conflict to outcompete one another by deploying diverse strategies for survival. Cutibacterium acnes is one of the most common bacterial species on human skin and can promote the common disease acne vulgaris. By employing a combined strategy of functional screening, genetics, and proteomics we discovered a strain of Staphylococcus capitis (S. capitis E12) that selectively inhibited growth of C. acnes with potency greater than antibiotics commonly used in the treatment of acne. Antimicrobial peptides secreted from S. capitis E12 were identified as four distinct phenol-soluble modulins acting synergistically. These peptides were not toxic to human keratinocytes and the S. capitis extract did not kill other commensal skin bacteria but was effective against C. acnes on pig skin and on mice. Overall, these data show how a member of the human skin microbiome can be useful as a biotherapy for acne vulgaris.
Assuntos
Acne Vulgar/terapia , Terapia Biológica/métodos , Pele/microbiologia , Staphylococcus capitis/imunologia , Simbiose/imunologia , Acne Vulgar/imunologia , Acne Vulgar/microbiologia , Adulto , Animais , Feminino , Humanos , Queratinócitos/imunologia , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Proteínas Citotóxicas Formadoras de Poros/isolamento & purificação , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Proteínas Citotóxicas Formadoras de Poros/toxicidade , Cultura Primária de Células , Propionibacterium acnes/imunologia , Propionibacterium acnes/patogenicidade , Pele/imunologia , Staphylococcus capitis/isolamento & purificação , Staphylococcus capitis/metabolismo , Suínos , Testes de Toxicidade , Adulto JovemAssuntos
Acne Vulgar/tratamento farmacológico , Curcumina/farmacologia , Propionibacterium acnes/imunologia , Transdução de Sinais/efeitos dos fármacos , Acne Vulgar/imunologia , Acne Vulgar/microbiologia , Curcumina/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/imunologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/imunologia , Células THP-1 , Receptor 2 Toll-Like/metabolismoRESUMO
Scutellariae radix, the root of Scutellaria baicalensis, has long been applied in traditional formulations and modern herbal medications. Propionibacterium acnes (P. acnes) in follicles can trigger inflammation and lead to the symptom of inflammatory acnes vulgaris. This study was aimed at evaluating the effect of Scutellariae radix extract and purified components isolated from it on inflammation induced by P. acnes in vitro and in vivo. The results showed the ethyl acetate (EA) soluble fraction from the partition of crude ethanolic extract from Scutellariae radix inhibited P. acnes-induced interleukin IL-8 and IL-1ß production in human monocytic THP-1 cells. Seven flavones were isolated from the EA fraction by repeated chromatographies, and identified as 5,7-dihydroxy-6-methoxyflavone (FL1, oroxylin), 5,7-dihydroxy-8-methoxyflavone (FL2, wogonin), 5-hydroxy-7,8-dimethoxyflavone (FL3, 7-O-methylwogonin), 5,6'-dihydroxy-6,7,8,2'-tetramethoxy flavone (FL4, skullcapflavone II), 5,7,4'-trihydroxy-8-methoxyflavone (FL5), 5,2',6'-trihydroxy-7,8-dimethoxyflavone (FL6, viscidulin II), and 5,7,2',5'-tetrahydroxy-8,6'-dimethoxyflavone (FL7, ganhuangenin). They all significantly suppressed P. acnes-induced IL-8 and IL-1ß production in THP-1 cells, and FL2 exerted the strongest effect with half maximal inhibition (IC50) values of 8.7 and 4.9 µM, respectively. Concomitant intradermal injection of each of the seven flavones (20 µg) with P. acnes effectively attenuated P. acnes-induced ear swelling, and decreased the production of IL-6 and tumor necrosis factor-α in ear homogenates. Our results suggested that all the seven flavones can be potential therapeutic agents against P. acnes-induced skin inflammation.
Assuntos
Anti-Inflamatórios/administração & dosagem , Flavonas/administração & dosagem , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Propionibacterium acnes/imunologia , Scutellaria baicalensis/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Flavonas/química , Flavonas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Camundongos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Pele/efeitos dos fármacos , Pele/imunologiaRESUMO
Most orally administered polyphenols are metabolized, with very little absorbed as aglycones and/or unchanged forms. Metabolic and pharmacokinetic studies are therefore necessary to understand the pharmacological mechanisms of polyphenols. Jumihaidokuto (JHT), a traditional Japanese medicine, has been used for treatment of skin diseases including inflammatory acne. Because JHT contains various types of bioactive polyphenols, our aim was to clarify the metabolism and pharmacokinetics of the polyphenols in JHT and identify active metabolites contributing to its antidermatitis effects. Orally administered JHT inhibited the increase in ear thickness in rats induced by intradermal injection of Propionibacterium acnes. Quantification by LC-MS/MS indicated that JHT contains various types of flavonoids and is also rich in hydrolysable tannins, such as 1,2,3,4,6-penta-O-galloyl glucose. Pharmacokinetic and antioxidant analyses showed that some flavonoid conjugates, such as genistein 7-O-glucuronide and liquiritigenin 7-O-glucuronide, appeared in rat plasma and had an activity to inhibit hydrogen peroxide-dependent oxidation. Furthermore, 4-O-methylgallic acid, a metabolite of Gallic acid, appeared in rat plasma and inhibited the nitric oxide reaction. JHT has numerous polyphenols; it inhibited dermatitis probably via the antioxidant effect of its metabolites. Our study is beneficial for understanding in vivo actions of orally administered polyphenol drugs.
Assuntos
Anti-Inflamatórios/farmacocinética , Antioxidantes/farmacocinética , Dermatite/tratamento farmacológico , Extratos Vegetais/farmacocinética , Polifenóis/farmacocinética , Propionibacterium acnes/imunologia , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/sangue , Antioxidantes/administração & dosagem , Dermatite/microbiologia , Flavanonas/sangue , Flavanonas/farmacocinética , Genisteína/sangue , Genisteína/farmacocinética , Masculino , Medicina Tradicional , Extratos Vegetais/administração & dosagem , Extratos Vegetais/sangue , Polifenóis/administração & dosagem , Polifenóis/sangue , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: Yashada bhasma (YB) and Tankana (TA) are well characterized minerals used in traditional medicine for the treatment of various skin ailments. Yashada bhasma and TA are a unique preparation of zinc and borax, respectively. The study was conducted to evaluate the in vitro inhibitory effect of YB, TA and its combination (YBTA) on Propionibacterium acne growth and P. acne-induced inflammation. METHODS: The minerals were tested for anti-P. acne activity by disc diffusion and broth microdilution methods. The effect of these minerals on P. acne induced TNF-α and IL-8 production and gene expression were studied in THP-1 cells. In vitro toxicity was tested on human keratinocytes (HaCaT) and mouse embryonic fibroblasts (NIH3T3) using MTT assay. RESULTS: The minimum inhibitory concentrations (MIC values) for YB, TA and YBTA against P. acne were 0.1 ± 0.2, 1.9 ± 0.5 and 0.3 ± 0.5 mg mL(-1) , respectively. YB, TA and YBTA inhibited TNFα by 57.57%, 59.09% and 68.93% and IL-8 production by 48.76%, 47.92% and 51.13% in P. acne-stimulated THP-1 cells, respectively. The CTC50 values on HaCaT and NIH3T3 was 17.44 ± 0.5 and 16.37 ± 0.2 µg mL(-1) for YB, 1023.03 ± 4.0 and 1286.17 ± 4.4 µg mL(-1) for TA and 89.12 ± 2.3 and 111.58 ± 3.5 µg mL(-1) for YBTA, respectively. CONCLUSION: The present study revealed the inhibitory effect of YB, TA and YBTA on P. acne growth and inflammation. Clinical studies have suggested the anti-acne benefits of formulations containing YB and TA. The findings obtained from the present in vitro studies provide evidence to support the mechanism of anti-acne properties of YB and TA.
Assuntos
Acne Vulgar/imunologia , Boratos/farmacologia , Infecções por Bactérias Gram-Positivas/imunologia , Propionibacterium acnes/imunologia , Óxido de Zinco/farmacologia , Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Animais , Boratos/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Interleucina-8/genética , Interleucina-8/imunologia , Queratinócitos , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , RNA/química , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Óxido de Zinco/uso terapêuticoRESUMO
In this study, we aimed to evaluate the inhibitory effect of wild bitter melons (WBM; Momordica charantia Linn. var. abbreviata Ser.) on Propionibacterium acnes-induced inflammation and to identify the bioactive components. Our results showed that ethyl acetate (EA) extract of WBM fruit in vitro potently suppressed pro-inflammatory cytokine and matrix metalloproteinase (MMP)-9 levels in P. acnes-stimulated THP-1 cells. Furthermore, concomitant intradermal injection of WBM EA extract in mice effectively attenuated P. acnes-induced ear swelling and granulomatous inflammation. To further investigate the bioactive components, we found that both saponifiable (S) and nonsaponifiable (NS) fractions of WBM EA extract significantly suppressed pro-inflammatory cytokine and MMP-9 levels. Phytol and lutein, identified in the NS fraction, also inhibited cytokine production. Moreover, S and NS fractions of EA extract, phytol and lutein, activated peroxisome proliferator-activated receptor (PPAR) α and ß in the transactivation assay. Our results suggested that PPARα or PPARγ signalling may contribute, at least in part, to the anti-inflammatory activity of WBM.
Assuntos
Anti-Inflamatórios/farmacologia , Infecções por Bactérias Gram-Positivas/imunologia , Momordica charantia/química , Extratos Vegetais/farmacologia , Propionibacterium acnes/imunologia , Animais , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Regulação para Baixo/efeitos dos fármacos , Frutas/química , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/isolamento & purificação , Propionibacterium acnes/fisiologiaRESUMO
18Beta-glycyrrhetinic acid (GA), the major bioactive component of licorice root extract, has a protective effect on hepatic injury and exhibits antiinflammatory activity. Here, we investigate the effect of GA in Propionibacterium acnes-induced acute inflammatory liver injury. C57BL/6 mice were primed with P. acnes followed by lipopolysaccharide challenge to induce fulminant hepatitis. GA (75 mg/kg) or vehicle control was administered intraperitoneally daily 1 day after P. acnes priming, and GA significantly improved mouse mortality. Then, to investigate the underlying mechanisms of GA in this acute inflammatory liver injury model, we primed C57BL/6 mice with P. acnes only. We propose that GA ameliorates acute P. acnes-induced liver injury through reduced macrophage inflammatory protein (MIP)-1alpha expression in Kupffer cells by down-regulating MyD88 expression and inhibiting NF-kappaB activation. Reduced MIP-1alpha expression lowered the recruitment of CD11c(+)B220(-) dendritic cell precursors into the liver. Consequently, GA treatment inhibits the activation and proliferation of liver-infiltrating CD4(+) T cells and reduces the production of serum alanine aminotransferase and proinflammatory cytokines such as interferon-gamma and tumor necrosis factor-alpha. Moreover, anti-MIP-1alpha treatment in P. acnes-primed mice inhibits the recruitment of dendritic cell precursors into the liver and suppresses mouse mortality as GA does. Taken together, our results suggest that GA exhibits antiinflammatory effects through inhibition of MIP-1alpha in a mouse model of acute P. acnes-induced inflammatory liver injury.
Assuntos
Anti-Inflamatórios/farmacologia , Quimiocina CCL3/imunologia , Ácido Glicirretínico/análogos & derivados , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Hepatite Animal/tratamento farmacológico , Células de Kupffer/imunologia , Falência Hepática Aguda/tratamento farmacológico , Propionibacterium acnes/imunologia , Animais , Anti-Inflamatórios/química , Antígeno CD11c/imunologia , Linfócitos T CD4-Positivos/imunologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Células Dendríticas/imunologia , Medicamentos de Ervas Chinesas/química , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Ácido Glicirretínico/química , Ácido Glicirretínico/farmacologia , Glycyrrhiza/química , Infecções por Bactérias Gram-Positivas/imunologia , Hepatite Animal/imunologia , Interferon gama/imunologia , Antígenos Comuns de Leucócito/imunologia , Lipopolissacarídeos/farmacologia , Fígado/imunologia , Falência Hepática Aguda/imunologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Camundongos , Fator 88 de Diferenciação Mieloide/imunologia , Raízes de Plantas/química , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Acne vulgaris is one of the most common skin diseases and can affect a large number of individuals at some point in their lives. Though the disease is multi-factorial, the Gram-positive, anaerobic bacterium Propionibacterium acnes (P. acnes), a member of resident skin microflora, is implicated in acne inflammation and associated with acne lesions. Common treatments such as antibiotic or benzoyl peroxide nonspecifically reduce bacteria population on the skin, which may disrupt homeostasis and cause further complications such as promoting growth of antibiotic-resistant bacteria strains. A component vaccine and an inactivated whole bacteria vaccine are made to target specifically P. acnes. The component vaccine targeting P. acnes surface sialidase and heat-inactivated P. acnes vaccine have both been shown to reduce P. acnes- induced inflammation in vivo and neutralize P. acnes in vitro, suggesting their potentials as new treatment for acne vulgaris. To facilitate acne studies, a bioengineering approach was utilized to design a new human acne model using tissue chamber. The tissue chamber of human sebocytes is shown to produce in mice a microenvironment similar to human acne inflammation. This approach can also be utilized in future studies in developing therapeutic acne vaccines and designing possible combined treatment of acne vaccine with alternative acne treatments.
Assuntos
Acne Vulgar/prevenção & controle , Vacinas Bacterianas/uso terapêutico , Propionibacterium acnes/imunologia , Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Acne Vulgar/terapia , Animais , Antibacterianos/uso terapêutico , Proteínas de Bactérias/imunologia , Cultura em Câmaras de Difusão , Avaliação Pré-Clínica de Medicamentos , Farmacorresistência Bacteriana Múltipla , Humanos , Camundongos , Neuraminidase/imunologia , Propionibacterium acnes/patogenicidade , Glândulas Sebáceas/citologia , Glândulas Sebáceas/microbiologia , Pele/microbiologia , Vacinas de Produtos Inativados , VirulênciaRESUMO
We investigated the effects of an extract of Radix Rosa laevigata (R. R. laevigata) on Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS)-induced acute liver injury. The plasma alanine aminotransferase (ALT) activity was significantly elevated by an intravenous injection of heat-killed P. acnes at a dose of 0.4 mg/mouse and then with LPS at 0.1 microg/mouse after 5 d. However, the elevated ALT activity was significantly reduced by the administered of R. R. laevigata (125 and 500 mg/kg/d) for 7 d before the LPS injection. In addition, the extract treatment reduced the number of liver mononuclear cells (MNCs), and malondialdehyde (MDA) and nitric oxide (NO) contents, but improved the liver oxygen radical absorbance capacity (ORAC) and mitochondrial membrane potential. Moreover, the chemical profile of R. R. laevigata was performed by high-performance liquid chromatography (HPLC) and the main peaks were identified as a series of polyphenol compounds which had been confirmed as the significantly active components by their anti-oxidative and NO inhibitory effects. These results suggest that the extract of R. R. laevigata offered good efficacy for preventing liver injury.
Assuntos
Lipopolissacarídeos/imunologia , Lipopolissacarídeos/toxicidade , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Propionibacterium acnes/imunologia , Rosa/química , Animais , Cromatografia Líquida de Alta Pressão , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Fígado/metabolismo , Fígado/microbiologia , Fígado/patologia , Hepatopatias/imunologia , Hepatopatias/microbiologia , Hepatopatias/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacosRESUMO
Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is a highly contagious lethal causative agent of swine pleuropneumoniae. Vaccines for this disease are usually serotype specific. In order to identify immunogenic genes specific to serotypes, two differentially expressed gene cDNA libraries of A. pleuropneumoniae CCVC259 (serotype 1) and CCVC263 (serotype 5) had been constructed by using a cDNA representational difference analysis (cDNA-RDA). From the libraries, six potential vaccine candidate genes expressed only in serotype 1 and 13 genes in serotype 5 were identified by antibody screening after gene expression in vitro with a ribosome display system. Eight sequences out of these exhibited 77-100% identity to the corresponding genes in Propionibacterium acnes. The antisera raised against A. pleuropneumoniae serotypes 1 and 5 were reactive with P. acnes at a titer of 1:6400 and vice versa (ELISA titer, 1:3200). Mice immunized with P. acnes were protected against 10 x LD50 challenge with A. pleuropneumoniae serotypes 1 and 5, and the survival rates were 90% and 95%, respectively. Pigs vaccinated with the P. acnes strain could develop high level antibody cross-reacted with A. pleuropneumoniae and obtain noticeable protection from A. pleuropneumoniae infection. These data demonstrate that there were common antigens between A. pleuropneumoniae and P. acnes, and the cross protectivity highlights the possibility of using P. acnes vaccines for preventing infection by A. pleuropneumoniae.
Assuntos
Infecções por Actinobacillus/imunologia , Infecções por Actinobacillus/veterinária , Actinobacillus pleuropneumoniae/genética , Actinobacillus pleuropneumoniae/imunologia , Vacinas Bacterianas/genética , Vacinas Bacterianas/imunologia , Propionibacterium acnes/imunologia , Doenças dos Suínos/imunologia , Animais , Anticorpos Antibacterianos/análise , Anticorpos Antibacterianos/biossíntese , Vacinas Bacterianas/efeitos adversos , Southern Blotting , Clonagem Molecular , DNA Complementar/biossíntese , DNA Complementar/genética , Avaliação Pré-Clínica de Medicamentos , Feminino , Genes Bacterianos/imunologia , Infecções por Bactérias Gram-Positivas/imunologia , Infecções por Bactérias Gram-Positivas/prevenção & controle , Masculino , Camundongos , Plasmídeos/genética , Plasmídeos/imunologia , Ribossomos/imunologia , Suínos , Vacinas de DNARESUMO
We have established an in vitro immunization protocol whereby human peripheral blood mononuclear cells (PBMCs) are initially treated with L-leucyl-L-leucine methyl ester (LLME) and subsequently sensitized with antigen in the presence of interleukin (IL)-2, IL-4, and adjuvant. This protocol resulted in the production of antigen-specific antibodies. PBMCs are potentiated to react with exogenous antigens upon treatment with LLME. We are using this system to investigate the immunomodulatory activity of additives. In the present study, we aimed to evaluate the immunomodulatory activity of Propionibacterium acnes (P. acnes), which is known to exhibit various immunomodulatory effects in murine models, using this in vitro immunization protocol. P. acnes was found to augment the production of antigen-specific antibodies by PBMC, possibly through increased production of inflammatory cytokines and/or increased T-B cell interaction. P. acnes hence appears to act as an adjuvant in the antibody response in in vitro immunization.
Assuntos
Adjuvantes Imunológicos/farmacologia , Formação de Anticorpos , Imunização/métodos , Leucócitos Mononucleares/imunologia , Propionibacterium acnes/imunologia , Adjuvantes Imunológicos/uso terapêutico , Terapia Biológica , Células Cultivadas , Dipeptídeos/farmacologia , Humanos , Interleucina-2/farmacologia , Interleucina-4/farmacologia , Leucócitos Mononucleares/efeitos dos fármacosRESUMO
The effect of silica treatment on the course of Babesia rodhaini infection was investigated in ICR mice pretreated with either a mixture of B. rodhaini parasitized red blood cell hemolysation-sonication (S) antigen and Propionibacterium acnes bacterin or P. acnes bacterin alone and not subjected to immunization. In the normal mice (non-immunized), the mean survival time was decreased by approximately 1 day when 5 mg per mouse of silica were intraperitoneally inoculated at 5 h before infection. In immunization with S antigen and P. acnes bacterin, all mice survived regardless of the dose of silica (15-25 mg per mouse) treatment. In contrast, in immunization with P. acnes bacterin alone, 3/10, 4/10 and 1/10 mice died of B. rodhaini, when inoculated with 15 mg per mouse, 20 mg per mouse and 25 mg per mouse of silica treatment 5 h before infection, respectively. These results suggest that peritoneal macrophages (M luminal diameter of), especially when activated non-specifically by P. acnes bacterin, play an important role in inhibiting multiplication of organisms at the early stage of infection and the mice immunized with S antigen were ready to quickly acquire an enhanced solid specific protection even if the function of M luminal diameter of was damaged by a high dose of silica treatment.
Assuntos
Babesiose/imunologia , Vacinas Protozoárias , Dióxido de Silício/farmacologia , Animais , Antígenos de Protozoários/imunologia , Babesia/imunologia , Babesiose/prevenção & controle , Vacinas Bacterianas/imunologia , Eritrócitos/parasitologia , Hemólise , Imunização , Ativação de Macrófagos , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Camundongos , Camundongos Endogâmicos ICR , Propionibacterium acnes/imunologiaRESUMO
The immunomodulatory effect of oxytetracycline (OTC) on murine splenic lymphocytes (MSL), peritoneal exudate macrophage (PEM) functions and antibody production was examined. In vivo exposure to OTC slightly delayed initiation of antibody formation during the primary response. However, OTC exposure had no effect on either the peak time of antibody response or peak antibody titer. OTC also had no significant effect on the secondary antibody response. Mitogen-induced proliferation of MSL cocultured with OTC and pokeweed mitogen, phytohemagglutinin or concanavalin was equivocal. However, allogeneic stimulation of MSL was inhibited at 100 micrograms/ml OTC. There was also a decrease in the number of cells recovered. OTC had no effect on lymphocyte cytotoxicity in cells cultured in vitro. OTC inhibited the cytotoxic response of Corynebacterium parvum-elicited PEM at 10 micrograms/ml (effector:target of 10:1). Low levels of OTC (1-10 micrograms/ml) augmented the cytotoxic response (effector:target of 5:1). The effect of OTC on induction of PEM cytotoxicity was assessed by coculturing thioglycollate-elicited (TG) PEM in vitro with IFN-gamma and endotoxin along with 0-100 micrograms/ml OTC. Induction of cytotoxicity was inhibited at 0.5 microgram/ml. The effect of OTC on TG-PEM antimicrobial activity was assessed by measuring reduction of nitroblue tetrazolium (NBT) and cytochrome C. OTC inhibited the reduction of NBT at 500 micrograms/ml following PMA stimulation of TG-PEM. OTC had no effect on either NBT or cytochrome C reduction following stimulation with opsonized zymosan. These results demonstrate that OTC-mediated immunosuppression is a multifaceted event, with differing sensitivities both between immune cells and between different pathways within the same cell.
Assuntos
Adjuvantes Imunológicos/farmacologia , Imunocompetência/efeitos dos fármacos , Oxitetraciclina/farmacologia , Animais , Formação de Anticorpos/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Propionibacterium acnes/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
A complex immuno-chemical treatment (immuno-stimulation, blockage of virus replication, interferon induction) was applied to 23 patients with warts and vegetations with various localisations. Results confirmed the treatment efficiency.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Antivirais/uso terapêutico , Condiloma Acuminado/tratamento farmacológico , Papillomaviridae , Infecções por Papillomavirus/tratamento farmacológico , Verrugas/tratamento farmacológico , Adolescente , Adulto , Antígenos Virais/uso terapêutico , Ácido Araquidônico/uso terapêutico , Biguanidas , Criança , Pré-Escolar , Corynebacterium , Quimioterapia Combinada , Feminino , Humanos , Lactente , Masculino , Morfolinas/uso terapêutico , Propionibacterium acnes/imunologia , Recidiva , Vitamina A/uso terapêuticoRESUMO
A group of 16 patients with ophthalmic zona zoster received antiviral and immunostimulating treatment with Romanian specific products. Results were spectacular. The problem of the identity of the varicella and zoster viruses is discussed.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Antivirais/uso terapêutico , Herpes Zoster Oftálmico/tratamento farmacológico , Adolescente , Adulto , Antígenos Virais/uso terapêutico , Ácido Araquidônico/uso terapêutico , Biguanidas , Corynebacterium , Avaliação de Medicamentos , Quimioterapia Combinada , Humanos , Pessoa de Meia-Idade , Morfolinas/uso terapêutico , Propionibacterium acnes/imunologia , Fatores de Tempo , Vitamina A/uso terapêuticoRESUMO
This study investigated the practicality and potential of the gerbil, Meriones unguiculatus, as a source of live Babesia divergens vaccine and also as a model for the use of the vaccine in cattle. A series of experiments with gerbils concerning vaccine infectivity, immunogenicity and safety were carried out. It was concluded that the use of RPMI medium/40% foetal calf serum as a diluent improved vaccine infectivity, but that the parasitaemia of the blood obtained from donor gerbils had little or no effect. The immunostimulants levamisole and killed Corynebacterium parvum improved vaccine immunogenicity and it was also shown that the subcutaneous route of infection resulted in the greatest host response. Control of vaccine virulence with drugs was only possible when drugs with prophylactic properties, such as imidocarb and long-acting oxytetracycline, were used. More studies are required on all these topics, particularly with regard to their applicability to cattle, and also concerning the possible attenuation of the parasite by manipulation in the gerbil host.
Assuntos
Babesiose/prevenção & controle , Doenças dos Bovinos/prevenção & controle , Modelos Animais de Doenças , Gerbillinae , Vacinação/veterinária , Adjuvantes Imunológicos , Animais , Babesia/imunologia , Babesiose/sangue , Bovinos , Doenças dos Bovinos/sangue , Diminazena/análogos & derivados , Diminazena/farmacologia , Feminino , Imidocarbo/farmacologia , Levamisol/imunologia , Masculino , Oxitetraciclina/farmacologia , Propionibacterium acnes/imunologia , Vacinas Protozoárias , Esplenectomia/veterinária , Virulência/efeitos dos fármacosRESUMO
During the 1970s, information obtained from animal tumor models and from patients with a spectrum of solid tumors indicated the worth of a variety of immunostimulating agents. These findings provided a biological and clinical rationale for conducting randomized trials to evaluate the worth of those agents. Consequently, in May 1977 the National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented a randomized trial to determine whether Corynebacterium parvum (C. parvum, CP) plus chemotherapy would be more effective than chemotherapy alone in prolonging the disease-free survival (DFS) and survival (S) of patients with primary operable breast cancer and positive axillary nodes. The results of that trial through 8 years of follow-up fail to indicate that treatment with CP used in conjunction with l-phenylalanine mustard (L-PAM) plus 5-fluorouracil (PF) results in a better DFS and S than that observed after chemotherapy alone. Use of the immunomodulator has instead resulted in a poorer, but not statistically significant, outcome. Despite adjustments made to account for any imbalance in distribution of prognostic factors between the two treatment groups and despite considering treatment compliance as a factor, the unfavorable outcome persisted. A high incidence of fever and chills was associated with the administration of CP. The administration of hydrocortisone before each CP treatment reduced the frequency of those and other systemic effects. The failure to demonstrate a benefit from CP is in keeping with the failure of other nonspecific stimulating agents to contribute to the creation of a new paradigm for the treatment of breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vacinas Bacterianas/uso terapêutico , Neoplasias da Mama/cirurgia , Propionibacterium acnes/imunologia , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Terapia Combinada , Avaliação de Medicamentos , Fluoruracila/administração & dosagem , Humanos , Metástase Linfática , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Cooperação do Paciente , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de SobrevidaRESUMO
Sodium diethyldithiocarbamate (DTC), mycobacterium cell wall extract (MCWE, Regressin), killed Corynebacterium parvum (C. parvum, Immunoregulin) and muramyldipeptide (MDP) were each combined with purified, live bovine rotavirus and inoculated into 3 month-old Holstein-Friesian calves in order to examine their ability to potentiate specific humoral and cellular immune responses. The vaccinated calves were boosted twice at 3 and 6 weeks after initial vaccine inoculation. The rotavirus was administered intramuscularly either in an aqueous suspension or in a water-in-oil (WIO) emulsion, prepared with incomplete Freund's adjuvant (IFA). DTC and C. parvum were given by the intravenous route, while MCWE and MDP were incorporated directly in the rotavirus suspension. Two groups of calves were also vaccinated either with rotavirus and IFA or with rotavirus emulsified in mineral oil and a mannide oleate compound (MOC, Montanide 888). A control group of calves was given phosphate-buffered saline (PBS) solution emulsified with IFA. The different vaccine preparations were then compared by studying the kinetics of serum rotavirus-neutralizing antibody production and of proliferative response by blood lymphocytes following in vitro stimulation with bovine rotavirus. The results showed that: (1) the bovine rotavirus should be incorporated in a WIO emulsion in order to induce a cell-mediated immune response as detected by the rotavirus-specific in vitro stimulation test with blood lymphocytes, and to produce higher neutralizing antibody titers in the serum; (2) the vaccines prepared with the mineral oil-MOC complex or IFA both induced comparable levels of humoral and cellular immune responses. The use of mineral oil and MOC as adjuvant may be preferred to IFA, because of the facility of preparing the vaccine and of the low viscosity of the resulting WIO emulsion: (3) the addition of MDP to the WIO emulsion prepared with IFA resulted in a higher cell-mediated immune response as determined by the in vitro blood lymphocyte transformation index specific for bovine rotavirus.
Assuntos
Adjuvantes Imunológicos , Anticorpos Antivirais/biossíntese , Ativação Linfocitária , Rotavirus/imunologia , Vacinas Virais/imunologia , Acetilmuramil-Alanil-Isoglutamina/imunologia , Animais , Bovinos , Parede Celular/imunologia , Ditiocarb/imunologia , Emulsões , Imunidade Celular , Injeções Intramusculares/veterinária , Injeções Intravenosas/veterinária , Cinética , Masculino , Óleo Mineral , Mycobacterium/imunologia , Mycobacterium/ultraestrutura , Testes de Neutralização , Propionibacterium acnes/imunologia , Vacinas Virais/administração & dosagemRESUMO
Mice were protected against subsequent infection with Schistosoma mansoni by intradermal or s.c. vaccination with killed schistosomula or soluble parasite extracts and bacillus Calmette-Guérin (BCG). Treatment with i.p. immunization was somewhat less effective, whereas i.m. vaccination failed to elicit protective immunity. The level of resistance induced by intradermal immunization was influenced by the strain of BCG used, and isolated BCG cell walls did not reliably substitute for whole BCG organisms as adjuvant. Bordetella pertussis vaccine and saponin were also able to function as adjuvants for protective immunity in this model, whereas other immunopotentiators including Corynebacterium parvum and aluminum hydroxide were ineffective. No correlation between resistance to challenge infection and antibody levels was detected. Animals immunized intradermally using either protective or non-protective adjuvants all showed minimal humoral reactivity against schistosomulum surface Ag but strong IgG response to soluble parasite components including paramyosin, which is the major serologically recognized Ag in mice vaccinated intradermally with schistosome Ag plus BCG and is protective in this model. In contrast, a strong correlation was observed between resistance and Ag-specific cell-mediated reactivity, including IFN production by T lymphocytes in vitro and macrophage activation in vivo. These results further substantiate the hypothesis that protection in this model is based on cell-mediated immune effector mechanisms. Moreover, they may be of general relevance in the design of vaccination protocols using other Ag or against other infectious agents.