Immunomodulatory activity of Toxicodendron pubescens in experimental models.

BACKGROUND: Toxicodendron pubescens is a botanical name of Rhus toxicodendron (Rhus tox). This plant is widely used in its homeopathically diluted form in the treatment of inflammatory and edematous conditions. In this study, various dilutions of Rhus tox including its crude form have been evaluated for their effects on immune response in the in vivo and in vitro experimental models. METHODS: Rhus tox in the form of mother tincture, 6cH, 30cH, 200cH and 1000cH dilutions was tested through in vivo models including sheep red blood cells (SRBCs) induced cellular and humoral immune response in C57/BL6 mice. The effects of Rhus tox dilutions were also evaluated in vitro on the functions of human polymorphonuclear (PMN) cells such as phagocytosis and intracellular killing of Candida albicans, chemotaxis, and reduction of nitroblue tetrazolium (NBT) dye. RESULTS: Rhus tox was found to intensify SRBCs induced antibody titer and delayed type hypersensitivity response in mice. Even higher dilutions such as 200cH and 1000cH were found to affect the immune response; however, the crude form, mother tincture, 6cH and 30cH dilutions revealed more potent effects than the 200cH and 1000cH dilutions. In in vitro assays, all the dilutions exerted stimulation of phagocytosis, candidacidal activity and chemotaxis of human PMN cells. The NBT dye reduction assay revealed that oxidative processes in the PMN cells are accelerated in the presence of Rhus tox. This study shows that Rhus tox possesses immunostimulatory activity in its crude form as well as in homeopathically diluted forms. These effects appeared to be concentration dependent as higher dilutions had less potent effects.

Evaluation of the immunological cellular response of Cebus apella exposed to the carcinogen N-methyl-N-nitrosourea and treated with CANOVA®.

The immune response modifier Canova® is a homeopathic remedy indicated for patients with depressed immune system, since this drug appears to increase adaptive immunity and induce an immune response against multiple and severe pathological conditions, including cancer. We evaluated the pattern of immune cellular response in non-human primates of the species Cebus apella exposed to N-methyl-N-nitrosourea (MNU) with and without Canova®. Twelve animals were divided into four groups, with three animals each: negative control and three experimental groups, MNU-alone (35 days); MNU (35 days)-plus-Canova® (3 days) and Canova®-alone (3 days). The animals received MNU orally and Canova® by three intravenous injections. Evaluation of the cellular immune response was performed by immunophenotyping of T-lymphocytes (CD4(+), CD8(+)), B-lymphocytes and natural killer cells. Analysis was also performed of the cell cycle. Our results suggest an increase of T-lymphocytes (CD4(+)CD3(+)) only in the Canova® group, while in the MNU-plus-Canova® group only B-lymphocytes increased.

Inmunidad celular en la patogénesis de la cardiopatía chagásica crónica / Cell-mediated immunity in the pathogenesis of chronic Chagas cardiomyopathy

Resumen La cardiopatía chagásica crónica se presenta en un 30% de las personas infectadas con Trypanosoma cruzi. Aunque el parásito puede ser controlado por la respuesta inmune después de la fase aguda, su detección se hace difícil en la fase crónica a pesar de la persistencia de éste en los tejidos de los individuos infectados. Dado que solo un porcentaje de estos individuos crónicamente infectados desarrolla el daño tisular, se sugiere la existencia de factores asociados que predicen la aparición de la sintomatología crónica: a) la genética del hospedero (moléculas del HLA), cuyo papel aún no se ha dilucidado, b) factores dependientes del parásito cómo la variabilidad de los genotipos (TcI a TcVI), su asociación con tropismo y daño tisular; y c) otros factores como la cantidad del inóculo, la reexposición constante a vectores infectados, las diferentes vías de infección y el estado inmunológico del hospedero. Varias teorías han sido implicadas en el compromiso cardiaco, como la persistencia del T. cruzi en los tejidos, la autoinmunidad inducida y el daño tisular producido por la respuesta inmune. En esta revisión se pretende emitir una hipótesis respecto a la disfunción celular inmune producida por la persistencia parasitaria en los tejidos y su papel en la patogénesis de la enfermedad. Se consideran aspectos como el pronóstico de los pacientes con cardiopatía chagásica llevados a trasplante de corazón por falla cardiaca avanzada comparado con otras causas de falla que conducen a trasplante y la posible organización de los infiltrados inflamatorios en el tejido cardiaco, el cual podría funcionar como un tejido linfoide terciario.

Abstract Chronic Chagas cardiomyopathy is present in 30% of people infected with Trypanosoma cruzi. Even though the parasite can be controlled by immune response after the acute phase, its detection is hard in the chronic phase despite its persistence in the tissues of infected individuals. Since only a fraction of these chronically infected individuals develop tissue damage, the existence of associated predictive factors for appearance of chronic symptoms is suggested: a) host's genetics (HLA molecules) whose role has not yet been clarified; b) parasitedependent factors such as genotype variability (TcI to TcVI), their association with tropism and tissue damage; and c) other factors like the amount of inoculum, the constant reexposure to infected vectors, the different infection routes and the host's immune status. Several theories have been put forward with regard to cardiac compromise, such as T. cruzi persistence in tissues, induce autoimmunity and tissue damage caused by immune response. This review intends to propose a hypothesis on cellular immune dysfunction produced by parasite persistence in tissues and their role in the pathogenesis of the disease. Aspects such as prognosis of patients with Chagas cardiomyopathy who undergo heart transplant due to advanced heart failure are taken into consideration and compared to other failure causes that lead to transplants, and also the possibly organisation of inflammatory infiltrates in heart tissue, which could function as a tertiary lymphoid tissue.

Influencia de la betarraga (Beta vulgaris var. cruenta) en el aumento de leucocitos, en ratones / Influence of beetroot (Beta vulgaris var. cruenta) on mice leukocytes increase

Introducción: La betarraga es una planta oriunda del Mediterráneo utilizada para fines alimenticios y medicinales. Contiene flavonoides. Objetivos: Determinar la influencia del consumo del extracto de Beta vulgaris var. cruenta en el incremento de leucocitos, en el ratón albino. Diseño: Estudio experimental. Lugar: Bioterio de la Institución Educativa 1182. Material biológico: Veinte ratones albinos de la cepa balb/c, machos, de peso promedio 24 g. Intervenciones: Se formó dos grupos, experimental y control, cada uno de diez ratones. Al grupo experimental se le administró vía oral extracto de Beta vulgaris var. cruenta en dosis de 250 mg/kg, volumen de 2 mL, cada cinco horas durante una semana, alternando con nutrientes, y al grupo control solo se le administró nutrientes. Principales medidas de resultados: Recuento de leucocitos. Resultados: Dentro del periodo de acondicionamiento, se observó un ligero incremento en la media de leucocitos del grupo control (3 681 ± 431,1) frente al grupo experimental (3 579 ± 473,5), cuya diferencia no fue significativa. Luego de administrar al grupo experimental el extracto de Beta vulgaris var. cruenta, alternando con sus nutrientes respectivos, se observó diferencia significativa de la media (7 961 ± 275,4) frente al grupo control (3 693 ± 414,7) (t student p<0,05). Conclusiones: En condiciones experimentales, el consumo del extracto de Beta vulgaris var. cruenta incrementó significativamente el número de leucocitos.

Background: Beetroot is a flavonoid-containing Mediterranean plant used for food and medicinal purposes. Objectives: To determine the influence of Beta vulgaris var. cruenta extract consumption in increasing albino mice leukocytes. Design: Experimental study. Setting: School Number 1182 bioterium. Biologic material: Twenty male Balb/c albino mice weighing 24 g average. Interventions: Two groups of ten mice each were formed; the experimental group received Beta vulgaris var. cruenta extract at 250 mg/kg oral doses, 2 mL volume every five hours for one week, alternating with nutrients; the control group received nutrients only. Main outcome measures: Leukocyte count. Results: During the conditioning period a slight increase in leukocytes in the control group (3 681 ± 431.1) was found compared to the experimental group (3 579 ± 473.5), but the difference was not significant. After administering Beta vulgaris var. cruenta extract alternating with nutrient media to the experimental group a significant difference in leukocytes (7 961 ± 275,4) was observed when compared with the control group (3 693 ± 414,7) (t student p<0,05). Conclusions: In experimental conditions, the consumption of Beta vulgaris var. cruenta extract significantly increased the number of leukocytes.

Cytotoxicity of leukocytes from normal and Shigella-susceptible (opium-treated) guinea pigs against virulent Shigella sonnei.

Intraepithelial lymphocytes were collected from the ileum of adult Hartley strain guinea pigs and used as effector cells in a 60-min bactericidal assay with virulent Shigella sonnei as target cells. Natural killer cytotoxicity (NKC) and antibody-dependent cellular cytotoxicity (ADCC) were measured and correlated with the resistance of the animals to infection by S. sonnei. Normal guinea pig intraepithelial lymphocytes exhibited mean NKC and ADCC values of 22.8 +/- 5.0 and 34.1 +/- 13.6, respectively. These animals were resistant to oral challenge with virulent S. sonnei. Intraepithelial lymphocytes from guinea pigs which were fasted for 4 days demonstrated NKC and ADCC values similar to those of normal animals (31.0 +/- 8.1 and 41.7 +/- 6.7, respectively). These animals also were resistant to oral challenge. Intraepithelial lymphocytes from guinea pigs which were given 1 ml of deodorized tincture of opium 2 h before cell collection demonstrated deficient NKC (4.7 +/- 4.2) and ADCC (5.3 +/- 4.9) values but remained resistant to infection by S. sonnei. When guinea pigs were fasted for 4 days and given opium, deficient NKC (2.0 +/- 2.0) and ADCC (1.3 +/- 1.3) values were demonstrated; this group of animals was susceptible to infection by S. sonnei (P less than 0.04). These experiments demonstrated that opium treatment depresses one form of gut immunity. When combined with starvation, opium treatment may increase susceptibility to infection by shigellae by modulation of immunity in addition to the effects on gut motility and bacterial flora.

[The effectiveness of paramunization for the control of feline coryza]. / Untersuchungen über die Wirksamkeit der Paramunisierung zur Bekämpfung des Katzenschnupfens.

20 cats in a cat home were treated prophylactically and therapeutically with Baypamun HK. The animals were allocated into three groups as described. 7 freshly admitted clinically healthy cats were treated prophylactically on day 1, 2 and 9 with 1 ml Baypamun HK (group I). 7 cats, who already were allocated for one year in the home and were sick of the feline respiratory disease complex were treated as described for group I (group II). 6 further cats, who also showed symptoms of the feline respiratory disease complex and had stayed for one year in the home were treated with physiol.saline solution according to group I (group III). From all cats blood samples were taken at day 1, 3, 10 and 17. The blood samples were checked for antibodies against feline calicivirus (FCV), feline herpesvirus (FHV), panleukopenia virus (PLV), feline peritonitis virus (FIPV) and feline immunodeficiency virus (FIV). Also the occurrence of the feline leukemia virus (FeLV) was evaluated. The cellular immunity was evaluated by means of the lymphocyte transformations test (LTT), nitroblue-tetrazolium reduction test (NBT) and cytochrome C-reduction test (CRT). Mean value and standard deviation was calculated from the results. The significance was determined by the t-test. The animals were examined clinically daily for 20 days for the feline respiratory disease complex. When necessary, the animals were treated by homeopathic and antibiotic products. At the time of admission to the home all cats were or had been treated with an attenuated panleukopenia vaccine. The serologic parameters were not influenced in the cats of group I.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of the glucocorticoid Oradexon on endotoxin-induced peritoneal cell response.

Glucocorticoids are important modulators of immune reactions. They are capable of antagonising several effects of the bacterial endotoxin by inhibiting endotoxin-induced leukocyte activation, and the production of cytokines and inflammatory mediators. We earlier demonstrated that the antiglucocorticoid RU 38486 enhances the cytokine production induced by endotoxin and aggravates the course of experimental endotoxic and septic shock. In the present study we investigated the effect of the glucocorticoid Oradexon on the endotoxin-induced peritoneal cell response. For measurement of the peritoneal cell response, male CFLP mice (20-25 g) were injected i.p. with 10 microg/10 g body weight endotoxin (E. coli 026:B6 LPS, Difco Lab, Detroit, lot 110273JB). Dexamethasone (Oradexon, N.V, Organon Oss, The Netherlands) was administered i.p., i.v. or s.c. in a dose of 0.1 mg/10 g body weight, alone or concomitantly with endotoxin. We found that bacterial endotoxin increased the total cell count due to neutrophilia at 24 hours and, due to increases in the number of macrophages and lymphocytes 48 and 72 hours after treatment, respectively. The i.p., i.v., and s.c. injection of Oradexon, increased the total cell count and the macrophage count at 24, 48 and 72 hours. The i.p., s.c. and i.v. injection of Oradexon, concomitantly with endotoxin, reduced the total cell count at 48 and 72 hours, due to decreases in the macrophage count. The i.p., i.v. or s.c. administration of Oradexon concomitantly with LPS decreased the lymphocyte count and the neutrophil count at 24 and 72 hours. These results prove that glucocorticoids are capable of modifying the immune cell reactions induced by endotoxin.

Bursine diluee: validation des hautes dilutions / Diluted bursin: validation of the high dilutions

L'article est une etape important vers la reconnaissance et la generalisation du concept d'immunomodulation a tres faibles doses developpe par le professeur M. Bastide il y a maintenant plus de 15 ans. La thymuline... (AU)

La inmunologia en la investigacion con altas dinamizaciones / Inmunology in research with high dilutions

Los modelos inmunologicos resultan de gran utilidad para demostrar la actividad de altas dinamodiluciones de hormonas o de mediadores. Se han empleado varios modelos experimentales. Describiremos sucesivamente: a accion de antigenos en alta dinamodilucion en la secrecion de anticuerpos especificos; la accion de moleculas en alta dinamodilucion que participan en el condicionamiento de linfocitos T o B, tal como hormonas timicas (linfocitos T) o bursina (linfocitos B); el efecto inmunomodulador de bajas dinamodiluciones de citokinas y la actividad inmunofarmacologica de silicea en alta dinamodilucion

De Hahnemann a la inmunologia actual / From Hahnemann to the actual immunology

Los conocimientos actuales sobre inmunologia, han llegado a las mismas conclusiones que el Dr. Samuel Hahnemann en 1813 expreso sobre la dermatitis por contacto y el Rhus toxicodendron. Los inmunologos, al estudiar los efectos de diferentes haptenos capaces de producir dermatitis por contacto, entre los que esta el Rhus toxicodendron, pudieron constatar que la inmunidad celular es la directamente responsable de la patologia manifiestal; asimismo, han demonstrado que los haptenos administrados por via oral a pequenas dosis provocan la proliferacion de linfocitos T supresores que limitan y regulan la respuesta celular. Es importante hacer notar que el Dr. Hahnemann desarrollo dentro de su terapeutica el uso del Rhus toxicodendron y que este medicamento se emplea en terapia homeopatica actual para curar padecimientos en los que la inmunidad celular es la responsable de las lesiones tisulares como son algunos cuadros de dermatitis por contacto, tuberculosis, enfermedades virales y artritis reumatoide. Los inmunologos han concluido conceptos que los llevan a la terapia homeopatica en lo que se refiere a la dermatitis por contacto; quedando por comprobar experimentalmente si en los otros padecimientos en donde se usa el Rhus toxicodendron tambien intervienen los linfocitos T supresores para impedir el dano a los tejidos

De Hahnemann a la inmunologia actual / From Hahnemann to the actual immunology

Los conocimientos actuales sobre inmunologia, han llegado a las mismas conclusiones que el Dr. Samuel Hahnemann en 1813 expreso sobre la dermatitis por contacto y el Rhus toxicodendron. Los inmunologos, al estudiar los efectos de diferentes haptenos capaces de producir dermatitis por contacto, entre los que esta el Rhus toxicodendron, pudieron constatar que la inmunidad celular es la directamente responsable de la patologia manifiestal; asimismo, han demonstrado que los haptenos administrados por via oral a pequenas dosis provocan la proliferacion de linfocitos T supresores que limitan y regulan la respuesta celular. Es importante hacer notar que el Dr. Hahnemann desarrollo dentro de su terapeutica el uso del Rhus toxicodendron y que este medicamento se emplea en terapia homeopatica actual para curar padecimientos en los que la inmunidad celular es la responsable de las lesiones tisulares como son algunos cuadros de dermatitis por contacto, tuberculosis, enfermedades virales y artritis reumatoide. Los inmunologos han concluido conceptos que los llevan a la terapia homeopatica en lo que se refiere a la dermatitis por contacto; quedando por comprobar experimentalmente si en los otros padecimientos en donde se usa el Rhus toxicodendron tambien intervienen los linfocitos T supresores para impedir el dano a los tejidos

Imunidade celular na Leishmaniose visceral / Cellular immunity in the visceral leishmaniosis

Com a finalidade de determinar a extensão e o mecanismo das anormalidades relativas à imunidade celular na leishmaniose visceral, 52 pacientes internados em diversos hospitais de Salvador com manifestações sugestivas da doença e todos com confirmação parasitológica (presença de leishmania em material aspirado da medula óssea) foram avaliados com os seguintes testes: a) Teste de transformação linfoblástica a mitogenos e antígenos; b) determinação das populações de linfócitos e sub-populações de linfócitos T; c) Avaliação da capacidade de produção de linfoquinas que aumentam a atividade microbicida dos macrófagos; d) Avaliação da capacidade de produzir interleucina e Y-interferon. Foram documentadas, no presente estudo, várias anormalidades relativas à imunidade celular: 1) Diminuição do número de linfócitos T no sangue periférico foi documentada em 13 (32,5 por cento) dos 40 pacientes em que se realizou o teste; em 04 de 10 casos estudados havia diminuição do percentual de células colaboradoras da resposta imunológica. No tocante à possível patogênese deste achado é mister destacar: a) a diminuição do número de linfócitos T não estava relacionada com a leucopenia destes doentes desde que não houve significância (p > 0.05) quando o número de linfócitos observados em pacientes com leishmaniose visceral foi comparado com o número de linfócitos de indivíduos sadios; b) anticorpos anti-linfocitários ou presente de substância séricas que inibissem o percentual real de linfócitos T não foram documentados no presente estudo; c) foi também afastada a possibilidade de que houvesse uma redistribuição linfocitária com aprisionamento de células em órgãos linfóides, desde quando depleção linfocitária em áreas T dependentes foi documentada no baço dos pacientes que faleceram...(AU)