Efeito de drogas inibidoras de TNF-α em células mononucleares do sangue periférico de indivíduos infectados pelo HTLV-I. / Effect of TNF-α inhibitors on peripheral blood mononuclear cells of HTLV-1- infected individuals.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2005

RESUMO

The human lymphotropic virus type I (HTLV-1) causes the HTLV-1 Associated Mielopathy Tropical Spastic Paraparesis (HAM TSP), Adult T-cell leukemia-lymphoma (ATL) and other systemic illnesses that are mediated by the immune response. HTLV-I induces a spontaneous proliferation of T-cells and pro-inflammatory cytokines. In individuals with HAM/TSP, the levels of TNF-α are elevated and are involved in tissue damage. TNF-α inhibitors may reduce inflammation and tissue damage in HTLV-1 associated diseases. The aim of this study was to evaluate the inhibitory effect of these drugs in PBMCs of 3 groups of HTLV-1 infected individuals: asymptomatic and sub-clinical carriers and thos with HAM/TSP. We tested four drugs with anti-TNF-α effect: Pentoxifilin, Forskolin, Rolipram and Thalidomide. The levels of TNF-α and IFN-γ were measured by the ELISA from supernatants of PBMC cultures without the addition of drugs spontaneous) and after the addition of drugs. We used PBMCs from 37 infected individuals: HAM/TSP (n=19), sub-clinical group (n=7) and asymptomatic (n=11). To evaluate the spontaneous production of TNF-α and IFN-γ we used the Mann-Whitney test and the results were compared between groups: TNF-α was higher in the HAM/TSP group than asymptomatic group p=0.001), HAM/TSP vs sub-clinical groups were not significant (p=0.75), sub-clinical vs asymptomatic individuals were significantly different p=0.005) as was the spontaneous production of IFN-γ in the HAM/TSP and asymptomatic groups (p=0.017). To evaluate the effect of TNF-α inhibitors, PBMC from individuals with spontaneous TNF-α and IFN-γ production higher than 50 pg/ml were utilized. Wilcoxon signed ranks test was used to evaluate to compare groups. The doses of Pentoxifilin were 50 and 200 M. The inhibition of TNF-α with 50 M of Pentoxifilin was 71 26% (p = 0.003,) and the inhibition of IFN-γ production with 50 M was 46 24% (p = 0.001) . We used Forskolin in doses of 50 and 200 M. The inhibition of TNF-α production with 50 M was 77 25% (p = 0.003) . The inhibition of IFN-γ with 50 M was 61 22% (p = 0.001) . Rolipram was used in doses of 1, 0.1 and 0.01M. The best inhibition of TNF-α production was achieved with 1 M of Rolipram, which inhibited 80 22% (p = 0.007).Rolipram inhibited 47 20% (p = 0.002) of the IFN-γ production with the minimal dose of 0.01 M. Doses of 1 and 50 M of Thalidomide were used. The 1M dose inhibited TNF-α production by 65 22% (p = 0.007). The inhibition of IFN-γ was less than 50% when the maximum dose was used. These results show that the drugs evaluated are able to suppress the production of TNF-α and IFN-γ and that this suppression is dose-dependent. This study also evaluated the serum levels of TNF-α and IL-6 in 38 HTLV-1 infected individuals, of which 18 had HAM/TSP and 20 were asymptomatic. The average of serum levels of TNF-α in the HAM/TSP group was 7 28 pg/ml; and in the asymptomatic group was 6 18 pg/ml. In both groups, only 1 result was positive, the others did not have detectable serum levels. The comparison between groups was not statistically significant (p = 0.840, Mann-Whitney). The average serum level of L-6 in the HAM/TSP group was 6 14 pg/ml. The comparison between groups was not statistically significant (p = 0.721, Mann-Whitney).

ASSUNTO(S)

vírus 1 linfotrópico t humano tnf-α imunologia human t-cell lymphotropic virus (htlv-1) tnf-α inibidores de tnf-α inhibitors ifn-γ ifn-γ

ACESSO AO ARTIGO

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