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1.
Arthritis Res Ther ; 10(1): R38, 2008 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-18380898

RESUMEN

INTRODUCTION: Our previous studies showed that arthritic Lewis (LEW) rats produced the highest levels of tumour necrosis factor (TNF)alpha in the recovery phase of adjuvant arthritis (AA), suggesting a correlation between high TNFalpha levels and reduced severity of arthritis. To further explore this correlation, we compared the TNFalpha secretion profile of the AA-resistant Wistar Kyoto (WKY) rats with that of LEW rats, determined the effect of exogenous TNFalpha on the course of AA in LEW rats, and examined various mechanisms involved in TNFalpha-induced disease modulation. METHODS: A cohort each of LEW and WKY rats was immunised subcutaneously with heat-killed Mycobacterium tuberculosis H37Ra (Mtb). At different time points thereafter, subgroups of rats were killed and their draining lymph node cells were tested for cytokine production. Another group of LEW rats was injected with TNFalpha intraperitoneally daily for a total of 10 injections, 3 before and 6 after Mtb challenge, and then observed for signs of AA. In parallel, TNFalpha-treated rats were examined for changes in other cytokines, in CD4+CD25+ T cell frequency, and in indoleamine 2,3-dioxygenase (IDO) mRNA expression levels. RESULTS: LEW rats displayed a TNFalpha secretion profile that was opposite to that of the WKY rats. Furthermore, TNFalpha treatment significantly down modulated the severity of AA in LEW rats, and decreased the interferon (IFN)-gamma secretion in response to the pathogenic determinant of the disease-related antigen. No significant alterations were observed in other parameters tested. CONCLUSION: The role of endogenous TNFalpha in the induction and propagation of arthritis is well established. However, exogenous TNFalpha can down modulate the course of AA, displaying an immunoregulatory functional attribute of this cytokine.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Experimental/prevención & control , Ganglios Linfáticos/metabolismo , Factor de Necrosis Tumoral alfa/uso terapéutico , Animales , Antirreumáticos/metabolismo , Artritis Experimental/inmunología , Citocinas/genética , Citocinas/metabolismo , Expresión Génica , Inyecciones Intraperitoneales , Masculino , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas Lew , Ratas Endogámicas WKY , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
2.
J Immunol ; 166(6): 4237-43, 2001 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-11238677

RESUMEN

Both genetic and environmental factors are believed to be involved in the induction of autoimmune diseases. Adjuvant arthritis (AA) is inducible in susceptible rat strains by injection of Mycobacterium tuberculosis, and arthritic rats raise T cell responses to the 65-kDa mycobacterial heat-shock protein (Bhsp65). We observed that Fischer 344 (F344) rats raised in a barrier facility (BF-F344) are susceptible to AA, whereas F344 rats maintained in a conventional facility (CV-F344) show significantly reduced incidence and severity of AA, despite responding well to the arthritogenic determinant within Bhsp65. The acquisition of protection from AA can be circumvented if rats are maintained on neomycin/acidified water. Strikingly, naive unimmunized CV-F344 rats but not BF-F344 rats raised T cell responses to Bhsp65 C-terminal determinants (BCTD) (we have previously shown that BCTD are involved in regulation of acute AA in the Lewis rat); however, T cells of naive CV-F344 and BF-F344 gave a comparable level of proliferative response to a mitogen, but no response at all to an irrelevant Ag. Furthermore, adoptive transfer into naive BF-F344 rats of splenic cells of naive CV-F344 rats (restimulated with BCTD in vitro) before induction of AA resulted in a considerably reduced severity of AA. These results suggest that spontaneous (inadvertent) priming of BCTD-reactive T cells, owing to determinant mimicry between Bhsp65 and its homologues in microbial agents in the conventional environment, is involved in modulating the severity of AA in CV-F344 rats. These results have important implications in broadening understanding of the host-microbe interaction in human autoimmune diseases.


Asunto(s)
Artritis Experimental/inmunología , Enfermedades Autoinmunes/inmunología , Proteínas Bacterianas , Chaperoninas/inmunología , Ambiente Controlado , Epítopos de Linfocito T/inmunología , Vivienda para Animales , Mycobacterium tuberculosis/inmunología , Linfocitos T/microbiología , Traslado Adoptivo , Animales , Artritis Experimental/epidemiología , Artritis Experimental/microbiología , Artritis Experimental/prevención & control , Enfermedades Autoinmunes/microbiología , Chaperonina 60 , Chaperoninas/administración & dosificación , Concanavalina A/inmunología , Susceptibilidad a Enfermedades , Epítopos de Linfocito T/administración & dosificación , Inmunidad Innata , Epítopos Inmunodominantes/administración & dosificación , Epítopos Inmunodominantes/inmunología , Incidencia , Inyecciones Intraperitoneales , Inyecciones Intravenosas , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Activación de Linfocitos , Masculino , Muramidasa/inmunología , Mycobacterium tuberculosis/crecimiento & desarrollo , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/inmunología , Ratas , Ratas Endogámicas F344 , Índice de Severidad de la Enfermedad , Especificidad de la Especie , Bazo/citología , Bazo/trasplante , Linfocitos T/inmunología , Linfocitos T/trasplante
4.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 13(3): 160-1, 133, 1993 Mar.
Artículo en Chino | MEDLINE | ID: mdl-8339036

RESUMEN

Osteal density of 189 Kidney Deficiency (KD) women displayed after menopause as determined by the method of gamma-ray absorption. The result showed that the osteal density of the KD women was significantly lower than those women of same ages without KD (P < 0.001) and the osteal density of the women whose menopause occurred before the age of 45 was lower than that after 45 (P < 0.05). This suggested that the prematurity of ovarial function and the decrease of estrogen ahead of time might be the cause. Therefore, the earlier the menopause, the lower the osteal density, as well as the more serious the KD well be.


Asunto(s)
Densidad Ósea , Menopausia/fisiología , Factores de Edad , Femenino , Humanos , Persona de Mediana Edad , Espectrometría gamma , Deficiencia Yang/fisiopatología
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