期刊
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
卷 44, 期 11, 页码 1134-1140出版社
ASSOC BRAS DIVULG CIENTIFICA
DOI: 10.1590/S0100-879X2011007500140
关键词
HTLV-1; TNF-alpha inhibitors; Pentoxifylline; Immune response
资金
- CNPq [1A]
- Fundacao de Amparo a Pesquisa do Estado da Bahia (FAPESB)
Human T lymphotropic virus type 1 (HTLV-1) is the causal agent of myelopathy/tropical spastic paraparesis (HAM/TSP), a disease mediated by the immune response. HTLV-1 induces a spontaneous proliferation and production of pro-inflammatory cytokines by T cells, and increasing interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) levels are potentially involved in tissue damage in diseases related to HTLV-1. This exaggerated immune response is also due to an inability of the natural regulatory mechanisms to down-modulate the immune response in this group of patients. TNF-alpha inhibitors reduce inflammation and have been shown to improve chronic inflammatory diseases in clinical trials. The aim of this study was to evaluate the ability of pentoxifylline, forskolin, rolipram, and thalidomide to decrease in vitro production of TNF-alpha and IFN-gamma in cells of HTLV-1-infected subjects. Participants of the study included 19 patients with HAM/TSP (mean age, 53 +/- 11; male: female ratio, 1:1) and 18 HTLV-1 carriers (mean age, 47 +/- 11; male: female ratio, 1:2.6). Cytokines were determined by ELISA in supernatants of mononuclear cell cultures. Pentoxifylline inhibited TNF-alpha and IFN-gamma synthesis with the minimum dose used (50 mu M). The results with forskolin were similar to those observed with pentoxifylline. The doses of rolipram used were 0.01-1 mu M and the best inhibition of TNF-alpha production was achieved with 1 mu M and for IFN-gamma production it was 0.01 mu M. The minimum dose of thalidomide used (1 mu M) inhibited TNF-alpha production but thalidomide did not inhibit IFN-gamma production even when the maximum dose (50 mu M) was used. All drugs had an in vitro inhibitory effect on TNF-alpha production and, with the exception of thalidomide, all of them also decreased IFN-gamma production.
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