INVESTIGADORES
MONTANER Alejandro Daniel
congresos y reuniones científicas
Título:
The immune system activity of severe trauma patient could be recovered by the immunostimulatory oligodeoxynucleotide imt 504
Autor/es:
JM RODRÍGUEZ, F ELÍAS, JC MARCHISIO, M LÓPEZ SALON, AD MONTANER, BC MASKIN, MP PEREIRO, CN ARTANA, JL DURGUERIAN, N PISTILLO
Lugar:
Buenos Aires. Argentina
Reunión:
Congreso; 9th Congress of the World Federation of Societies of Intensive and Critical Care Medicine; 2005
Institución organizadora:
World Federation of Societies of Intensive and Critical Care Medicine
Resumen:
Background: Many severe trauma patients show a depression of the immune functions. An example of this is the decrease in monocyte and lymphocyte functional capacities. This phenomenon is believed to play a role in the augmented susceptibility to secondary infections typical of these patients. We have previously shown the immunostimulating capacity of a new class of immunostimulatory oligodeoxynucleotides (ODNs) PyNTTTTGT on B lymphocytes and plasmacytoid dendritic cells from primates and rats (J. Immunol., 2003, 171: 3697-3704 and Vaccine, 2005, 23 (27): 3597-3603). The PyNTTTTGT prototype ODN was named IMT504. Objective: To evaluate “in vitro" the ability of ODN IMT504 to recover the functional capacity of the immune system cells from patients with severe trauma. Methods: Monocytes and lymphocytes from whole blood samples obtained from patients with severe trauma and from healthy volunteers at entry were studied. In order to evaluate the immune state of severe trauma patients, we studied the expression of HLA-DR on CD14 positive cells, CD40 on CD19 positive cells and IL6 in sera. On the other hand, in order to find out if the ODN IMT504 was able to immunostimulate white blood cells of severe trauma patients, the CD40 expression on CD19 positive cells (B lymphocytes) after a 48-hour incubation with IMT504 “in vitro” was studied. Results: Thirteen patients were enrolled in the study. APACHE II score (at entry): 22.5 (16-31), SOFA score (at entry): 6 (10-15). Mortality at 28 days: 46 %. Immune depression status of trauma patients was confirmed at entry, by a significant reduction in HLA-DR expression (expressed in % of positive cells) compared to healthy donor cells: 44.28 ± 12.28 % vs. 80.34 ± 12.16 %, p=0.0006. Moreover, CD40 on B lymphocytes (expressed by the geometric mean of fluorescence intensity, MFI) was also lower in patient samples: 95 ± 26 than in control cells: 134 ± 23 Gm, p = 0.01. After a 48-h culture with IMT504, MFI significantly increased in patient cells to 364 ± 148(p=0.00001). Conclusions: Both the results here presented and bibliographic data have shown that monocytes and B lymphocytes are affected in severe trauma patients. However, when the patient cells were incubated with the immunostimulatory ODN IMT504 they seem to recover their immunocompetence as measured by the levels reached by CD40 expression after treatment. These observations are encouraging and suggest the possible therapeutic use of the immunostimulatory ODN IMT504 on severe trauma patients to avoid eventual secondary infections and further complications.