RESUMO
To evaluate immune cell activation in patients with melioidosis, serum samples were assayed for interferon-gamma (IFN-gamma), soluble interleukin-2 receptors (sIL-2R), and soluble CD8 protein (sCD8). Forty patients with sepsis (23 fatal cases, 17 survivors) and 13 with localized disease were studied during acute illness; 12 additional patients were studied after discharge while on maintenance antimicrobial therapy. Serum concentrations of IFN-gamma and sIL-2R were greatly elevated, but sCD8 concentrations were not. These levels increased with disease severity and were associated with fatal outcomes. Macrophage activation by high concentrations of the cytokine IFN-gamma may contribute to pathophysiology and death in septicemic patients. Both IFN-gamma and sIL-2R seem to be predictive of outcome in patients with severe melioidosis and may prove useful in detection of relapse.
Assuntos
Antígenos CD/sangue , Antígenos de Diferenciação de Linfócitos T/sangue , Interferon gama/sangue , Melioidose/imunologia , Receptores de Interleucina-2/sangue , Adolescente , Adulto , Idoso , Antígenos CD8 , Criança , Pré-Escolar , Humanos , Imunidade Celular , Ativação de Macrófagos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sepse/imunologiaRESUMO
Patients with acute Plasmodium falciparum malaria have defective cell-mediated immune responses to malaria-specific Ag (MA). This immunologic defect may partially explain the difficulty with which natural immunity to falciparum malaria develops and may have important implications for the efficacy of potential malaria vaccines in endemic areas. To investigate the basis of this immune defect, we have examined the capacity of PBMC from patients with acute falciparum malaria to produce IL-2 and to express I1-2R in response to Ag stimulation. The effect of exogenous IL-1 and IL-2 on lymphocyte proliferation was studied. Soluble IL-2R levels were measured in acute and convalescent sera. Our results showed that no detectable IL-2 was produced and no IL-2R were expressed by PBMC in response to MA during the acute infection. IL-2 production and IL-2R expression were also depressed when PBMC were exposed to streptococcal Ag. The specific immune defect was not reconstituted by the addition of graded doses of purified human IL-1 or IL-2 and could not be attributed to suppressor adherent cells. In contrast to the absence of IL-2 and cell-bound IL-2R, circulating soluble IL-2R was elevated in acute sera. These findings suggest that the lack of IL-2, through either a defect in its production or inhibition of its activity, may be the basis of the Ag-specific immune unresponsiveness in acute P. falciparum malaria.
Assuntos
Tolerância Imunológica , Interleucina-2/biossíntese , Malária/imunologia , Plasmodium falciparum/imunologia , Doença Aguda , Adolescente , Adulto , Animais , Antígenos de Protozoários/imunologia , Separação Celular , Humanos , Interleucina-1/farmacologia , Interleucina-2/farmacologia , Linfócitos/imunologia , Linfócitos/metabolismo , Malária/sangue , Pessoa de Meia-Idade , Receptores de Interleucina-2/metabolismo , Estreptodornase e Estreptoquinase/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
Con A-pretreated mononuclear (MNC) cells from Thai adults with naturally acquired P. falciparum or P. vivax malaria were significantly less effective in suppressing the responsiveness of autologous or normal allogeneic responder cells to mitogenic lectins or allogenic stimulator cells than pretreated cells from healthy donors. Serial studies of three patients demonstrated that reduced suppressor cell activity was present early in malaria infection but returned to normal soon after treatment. These studies demonstrate that the loss of T cells previously observed in patients with malaria, in part may functionally represent a loss of suppressor T cells.
Assuntos
Malária/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Concanavalina A/farmacologia , Humanos , Teste de Cultura Mista de Linfócitos , Malária/sangue , Malária/tratamento farmacológico , Masculino , Fito-Hemaglutininas/farmacologia , Plasmodium falciparum , Plasmodium vivax , TailândiaRESUMO
The effect of mefloquine-HCL, a new 4-quinoline methanol anti-malarial compound, on in vitro blast transformation of human peripheral blood mononuclear cells (MNC) was studied. Mefloquine significantly suppressed lectin-induced blast transformation of MNC from healthy Thai adults but MNC responsiveness in the mixed leucocyte reaction (MLR) and cellular viability were not reduced by the concentrations of mefloquine studied. Both T and non-T MNC responsiveness was lower in cultures containing the drug than in normal control cultures. The addition of serum from individuals on mefloquine chemoprophylaxis caused no significant suppression in the blast transformation assays or the MLR but the data do not rule out any clinically significant in vivo suppressive effect by mefloquine on human cellular immune response.