RESUMEN
BACKGROUND: Severe injury causes immunological changes that may contribute to a poor outcome. Longitudinal characterization of lymphocyte response patterns may provide further insight into the basis of these immunological alterations. METHODS: Venous blood obtained seven times over 2 weeks from 61 patients with injury severity scores above 20 was assessed for lymphocyte phenotypic and activation markers together with serum levels of interleukin (IL) 2, IL-4, soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4), soluble CD8 (sCD8) and interferon gamma. RESULTS: Severe injury was associated with profound changes in the phenotypic and activation profile of circulating lymphocytes. Activation was indicated by increased numbers of T cells expressing CD25, CD69 and CD71, and raised serum levels of IL-2, sIL-2R, sCD4 and sCD8. Relatively higher levels of sIL-2R and sCD4 were found in patients with sepsis syndrome. CONCLUSION: Polytrauma is associated with dramatic alterations in the phenotypic and activation profile of circulating lymphocytes which are generally independent of clinical course. In contrast, several lymphocyte soluble factors, including sCD4 and sIL-2R, paralleled the clinical course. These data provide new insight into lymphocyte responses after injury and suggest that further assessment of soluble factors as clinical correlates, including those related to lymphocyte activation or generalized inflammation, may be warranted.
Asunto(s)
Citocinas/metabolismo , Activación de Linfocitos/inmunología , Proteínas de la Membrana/metabolismo , Linfocitos T/inmunología , Heridas y Lesiones/inmunología , Adulto , Antígenos CD/metabolismo , Femenino , Humanos , Hipersensibilidad Tardía/inmunología , Recuento de Leucocitos , Subgrupos Linfocitarios/inmunología , MasculinoRESUMEN
Several iron chelators, 3-hydroxypyridin-4-ones (CP) and desferrioxamine (DF) were compared for their effect on DNA synthesis, cell viability and expression of cell proliferation markers. Short-term (4 h) exposure of human peripheral blood mononuclear cells to CP or DF inhibited the proliferative response of cells to concanavalin A (Con A). Inhibition by CP and DF showed a dose-dependent effect with CP compounds more active than DF. Increased inhibitory activity of CP over DF was partly due to the lipophilic properties of CP. Pre-saturation of CP and DF with exogenous ferric ion either diminished or prevented the inhibitory effect. At high chelator concentrations or prolonged (72 h) exposure of the cells to chelators, inhibition occurred but poor cell viability was observed. In contrast to their inhibition of DNA synthesis, these iron chelators showed little effect on protein synthesis and the expression of transferrin receptors and interleukin-2 (IL-2) receptors. These findings suggest that both DF and CP compounds exert their effect by chelation of ferric ion with subsequent inhibition of DNA synthesis.