RESUMO
The ABL tyrosine kinase inhibitor imatinib mesylate is highly effective in the treatment of CML and is increasingly used in the stem cell transplantation (SCT) setting. Since ABL-dependent intracellular signaling molecules are involved in T-cell activation, imatinib may affect T-cell responses in vivo, thus affecting T-cell function in CML patients, disrupting immune reconstitution after allogeneic SCT and/or impeding the graft-versus-leukemia effect. Here we demonstrate that imatinib inhibits PHA-induced proliferation of normal peripheral blood mononuclear cells at in vitro concentrations (1-5 micromol/l) representative of the pharmacological doses used therapeutically in vivo. The effect is not dependent on antigen-presenting cells because CD3/CD28-induced T-cell stimulation was similarly inhibited by imatinib. Dose-dependent inhibition of the proliferative response of purified CD8+ and CD4+ T lymphocytes to anti-CD3/CD28 was similarly observed and associated with reduction in IFN-gamma production. The inhibitory effect could not be ascribed to an increased rate of apoptosis but the expression of activation markers on CD3+ T cells was significantly reduced in the presence of imatinib (1-5 micromol/L). Inhibition of T-cell proliferation was reversible after removal of the drug from the cultures. Thus, imatinib inhibits T-cell proliferation in vitro, an effect that is APC-independent, reversible, and does not involve apoptosis induction.
Assuntos
Ativação Linfocitária/efeitos dos fármacos , Piperazinas/farmacologia , Pirimidinas/farmacologia , Linfócitos T/efeitos dos fármacos , Benzamidas , Células Sanguíneas , Complexo CD3/análise , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Mesilato de Imatinib , Proteínas Oncogênicas v-abl/antagonistas & inibidores , Fito-Hemaglutininas/farmacologia , Linfócitos T/imunologiaRESUMO
Herpes simplex virus encephalitis (HSVE) is associated with a high mortality rate and a high probability of neurological sequelae. Good results are obtained when HSVE is promptly diagnosed and treated with acyclovir. We present a 71-year-old woman with clinically diagnosed HSVE, confirmed by PCR detection of HSV-1 DNA in the cerebrospinal fluid. She was treated with acyclovir (30 mg/kg day) for two weeks. Clinical and neuropsychological assessments 6 months after admission were normal; however MRI at 2, 6 and 12 months showed progressive deterioration with extensive white matter and cortical damage. Imaging studies of a cohort of patients surviving PCR-confirmed HSVE are needed to determine whether this pattern is occasional or a frequent form of progression.