RESUMO
AIMS: To determine whether immunotherapy with heat-killed, selected Actinomycetales species could influence the progression of spontaneous Type 2 diabetes mellitus and obesity in a rat model. MATERIALS & METHODS: Preparations of either Gordonia bronchialis, Tsukamurella inchonensis or a saline placebo were given by three subcutaneous injections, 30 days apart, starting when rats were aged 120 days, just before development of Type 2 diabetes mellitus, and at day 440, when the disease was well established. Bodyweight, blood sugar, cholesterol, triglycerides and insulin levels were measured to determine the effects and at the end of the experiments, animals were subjected to necropsy. RESULTS: The development of Type 2 diabetes mellitus was prevented by both reagents, most effectively by T. inchonensis. In the treatment experiment, the effects of the disease were reduced by both treatments, markedly so by T. inchonensis. In both experiments obesity was reduced in treated animals. The possible mechanisms of action are discussed. CONCLUSION: Our findings suggest that Type 2 diabetes mellitus in the studied rats is associated with obesity, and that both diabetes and obesity can be prevented or improved by treatment with Actinomycetales immune modulators.
Assuntos
Actinomycetales/imunologia , Misturas Complexas/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Imunoterapia , Obesidade/tratamento farmacológico , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Misturas Complexas/efeitos adversos , Misturas Complexas/imunologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/imunologia , Modelos Animais de Doenças , Progressão da Doença , Humanos , Insulina/sangue , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/microbiologia , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/imunologia , RatosRESUMO
AIMS: Can heat-killed, borate-buffered suspensions of Gordonia bronchialis, Rhodococcus coprophilus or Tsukamurella inchonensis be used to treat canine flea allergy? MATERIALS & METHODS: Organisms cultured on Sauton's medium into stationary phase were autoclaved in borate-buffered saline and stored at 10 mg wet weight/ml. Intradermal injections of 0.1 ml containing 1 mg of bacilli were administered on the first and 20th days of the study. G. bronchialis and R. coprophilus were most effective in a pilot study of a small number of dogs with flea allergy. A larger number of affected dogs were then randomized to receive placebo or either of the two selected reagents. The extent and severity of allergic signs and symptoms were scored and blood samples were collected just before the first injection and 28 days after the second. RESULTS: Both selected reagents reduced the extent and severity of lesions (p < 0.001) and reduced scratching. Eosinophil numbers were reduced (p < 0.0001) between the first and second assessment. CONCLUSIONS: Injections of G. bronchialis or R. coprophilus effectively reduce the signs and symptoms of flea allergy in dogs.
Assuntos
Actinomycetales/imunologia , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Imunoterapia , Preparações Farmacêuticas/administração & dosagem , Actinomycetales/metabolismo , Alérgenos/imunologia , Animais , Contagem de Células , Progressão da Doença , Cães , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Eosinófilos/patologia , Hipersensibilidade/fisiopatologia , Imunomodulação , Preparações Farmacêuticas/metabolismo , Saliva/imunologia , Sifonápteros/imunologia , Equilíbrio Th1-Th2RESUMO
This article describes the first use of heat-killed, borate-buffered preparations of aerobic actinomycetales to immunize pregnant animals in order to determine the effect on their pregnancy and fertility and the survival coefficients of their offspring. Pregnant rats received three injections of Gordonia bronchialis, Rhodococcus coprophylus or physiological saline and a proportion of their offspring were challenged with live Trypanosoma cruzi at the time of weaning. Levels of parasitemia and, in some animals, of the cytokines IFN-Î³ï© and IL-10 were measured. The progress of pregnancy, fertility and survival of offspring were unaffected by the maternal immunizations. The offspring of rats immunized with G. bronchialis displayed significantly reduced parasitemias, with increased levels of IFN-γ and reduced levels of IL-10, 4 days after challenge. The offspring of rats immunized with R. coprophylus displayed greater parasitemias than did those of the control group. These unexpected results are discussed and their causation considered.
Assuntos
Actinomycetales/imunologia , Doença de Chagas/prevenção & controle , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/imunologia , Parasitemia/prevenção & controle , Trypanosoma cruzi/patogenicidade , Animais , Anticorpos Antiprotozoários/sangue , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Modelos Animais de Doenças , Feminino , Bactéria Gordonia/imunologia , Interferon gama/sangue , Interleucina-10/sangue , Masculino , Troca Materno-Fetal , Parasitemia/imunologia , Parasitemia/parasitologia , Gravidez , Ratos , Rhodococcus/imunologiaRESUMO
The well-established model of Chagas' disease in "l" rats was used to evaluate the effects of three injections of heat-killed Gordonia bronchialis, Rhodococcus coprophilus or saline on Trypanosoma cruzi parasitaemia and acute and chronic myocarditis, sequelae of the infection. Two vaccinating injections were given prior to challenge with T. cruzi, and the third, immunotherapeutic, injection was given 7 days after challenge. Treatment with either actinomycete significantly reduced acute parasitaemia (p<0.04), modified cellular infiltration during acute myocarditis and limited chronic myocarditis (p<0.03) in comparison with the saline-treated control animals. Immunological investigations showed that both bacterial preparations achieved their results through different mechanisms. The relevance of our findings to human Chagas' disease is discussed.