Influência do envelhecimento no perfil de síntese de citocinas em indivíduos portadores da infecção crônica pelo schistosoma mansoni

• Ano de defesa: 2004
• Autor(a) principal: Elaine Speziali de Faria
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Bioquímica e Imunologia; Esquistossomose Aspectos imunológicos; Bioquímica
• Link de acesso: http://hdl.handle.net/1843/BUBD-9GAEW7

The immunosenescence have been well described in humans and in a variety of animal species presenting large influence on the immune system functional changes which can be observed both in lymphoid organs and in cell components of immune system. It was demonstrated, for example, changes on the phenotype, repertoire and lymphocyte activation, as well as on the cytokine profile produced by this cells. There are also a strong association between the resistance to Schistosoma sp. helminthic infection and reinfection and senescence. In human schistosomiasis, for example, the worm burden increase in the two first decades of life. These same individuals, from the age of 30, show a progressive decline in the intensity of infection that could be due to the presence of immunomodulatory mechanisms. Schistosomiasis is a chronic disease and overlap to the aging process. This study, we assess the influence of the immunological changes that occur during senescence in human schistosomiasis. Individuals between 10 and 95 years old, of both gender, living in endemic area, were segregated in four groups of age (10-24; 25-49; 50-69 e 70-95). In each group, the subjects were categorized according the worm burden in either no eggs in faeces or more than 100 eggs/g of faeces. Individuals that presented no egg in faeces exam belonging to the same age group, described above, were considered our control group. We analyzed, with flow cytometry, the cytokine profile produced by periferic blood leucocytes (NK cells, B lymphocytes, T cells CD4+ and T cells CD8+) after 5 hours of in vitro incubation with either no stimuli or specific antigen stimulation (SEA or SWAP). When we analyzed the total leucocytes of periferic blood, we observed, in non-stimulated culture, that aging is associated to the increase of the frequency of leucocyte producing IL-10 from elderly infected and not infected, suggesting a greater ability to modulate the infection than young subjects. Moreover, we also observed, together to the increased of IL-10, the increase on the frequency of IL-2 in the leucocytes from older infected individuals (70 to 95 years old), suggesting the gain on the cellular reactivity or cell apoptosis. The cytokine profile produced by NK cells, B lymphocytes, T cells CD4+ and T cells CD8+, not stimulated, shows also very altered with aging. We observed that, in younger ages, there are a strong participation of the T CD8 lymphocytes characterized by the increase of IL2+,IFN- +,IL-4+ cells. With infection, this profile changes, taking a decrease of this IL-2 and IL-4 positive cells, but keeping the high percentage of IL-10 and IFN- positive cells. With aging process, we observed a different profile. There is a important contribution of the TCD4 cells characterized by the increase of IL-10+ e IFN- + cells. In the infection context, we noted a strong contribution of both the subpopulation of lymphocytes. It occurs a decrease of T CD4+IL-10+ and IFN- + cells and the increase of CD4+IL-2+ cells. Regarding to the TCD8+ lymphocytes, occurs a slight decrease of IL-4+ and IFN- + cells and an increase of the CD8+ IL-10+ cells in this age. With either the SEA-stimulation or SWAP-stimulation, the infected elderly (70 to 95 years old) showed an increase on the CD16+IFN + cells percentage that was not observed in negative elderly (70 to 95 years old), and, a decrease on the B cells percentage IL-10 positives. The results shows that the differences are located in the extremes of lifetime. The adults subjects between 25 and 69 years old presents stables pattern of cytokine synthesis. However, outstanding differences on the positive cytokine pattern to CD4+, CD16+ and CD8+ cells were observed in negative and infected individuals over 70 years old. This data strongly suggest that the immunological changes found are aging-related. In addition, the maintenance of the high percentage of IL-10 (even that produced by different cells populations) in the elderly infected individuals probably is directed related to the induction of immunomodulatory mechanisms typical of the chronic phase of infection. We can say that aging has a strong effect on the percentage of cytokine and on the immunity to the S. mansoni infection.