Avaliação de alguns aspectos da resposta imune tipo celular em animais portadores do tumor ascitico de Ehrlich e tratados com titanocenos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2002

RESUMO

In this work, as a continuation of previous studies in our laboratory, we investigated the effects of the titanocene dicyclopentadienyldichlorotitanium IV compound, DDCT, (15 mg/kg/day/ per two days) on the natural killer cell activity (NK) and on Th1 [interleukin (IL)-2 and interferon-g (IFN-g)] and Th2 (IL-4 and IL-10) responses in normal and Ehrlich ascites tumor (EAT)-bearing mice. Moreover, for comparative effect, we also studied the dicyclopentadienylditiocianatetitanium IV, BCDT. The structural difference between these compounds is the substitution of the halides halogens present in DDCT by pseudo halogens in BCDT. With the BCDT compound, besides the immunological parameters mentioned above, we evaluated the effect of the treatment using one, two or three doses of BCDT (10, 15 or 30 mg/kg/day) on the growth and differentiation of granulocyte-macrophage progenitor cells [colony-forming units of granulocyte-macrophage (CFU-GM)], of normal and EAT-bearing mice. As studied previously with the DDCT compound, we also evaluated the bone marrow cellularity, the presence of colony stimulating factors (CSFs) and survival of these animals. Our results demonstrated that the DDCT compound is more effective than the BCDT one. In despite of the differences found, we observed that these compounds share the ability of regulating positively the hematopoietic and immunologic unbalance during the EAT evolution. As expected for the EAT-model, concomitant myelosuppression, increased number of spleen CFU-GM and changes in bone marrow cellularity were observed. The treatment of EAT-bearing mice with BCDT produced a dose-dependent increase in myelopoiesis, a reduction in splenic colonies and a restoration of the total and differential marrow cell counts. In addition, BCDT treatments also increased the survival of these animals. The most effective dose schedule was 10 mg/kg/day/per three days, which, in normal animals, also produced increased bone marrow CFU-GM numbers along with a CSF production boost. High doses of BCDT cause toxic effects and induced extramedular hematopoiese. Regarding the production of cytokines, the treatment with the titanocene compounds blocked the Th1-Th2 polarization found during the EAT progression. In this respect, the treatment of these animals with DDCT (15 mg/kg/day/per two days) or BCDT (10 mg/kg/day/per three days) increased the IL-2 levels, regulated the atypical IFN-g secretion positively and reduced the levels of IL-10, increased during the temporal evolution of EAT. In relation to the functional activity of NK cells, the treatment with both compounds enhanced the NK cell function, reduced during the EAT growth. Only the DDCT compound rescued to normal values the activity of NK cells. These up-modulatory effects demonstrated in this study, specially using the DDCT compound, indicated a new aspect of the antitumoral action mechanism of the titanocenes. Thus, it is encouraging, in this context, to consider these compounds for combination chemotherapy, protecting the host from hematotoxicity as well as supplementing tumoricidal efficacy

ASSUNTO(S)

celulas killer hematopoese perinatologia

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