Evaluación de la acción del ODN IMT 504 en un modelo Experimental de sepsis en ratas Sprague Dawley

PEREIRO M; ELÍAS F; DE NICHILO A; RODRIGUEZ JM; MONTANER A; ARTANA A; LAGO N; MIRABELLI C; RIETSCHEL V; BRUNO S; FLO J; LÓPEZ R; ZORZOPULOS J; MASKIN M

Mar del Plata

Congreso; Congreso Argentino de Terapia Intensiva; 2010

Sociedad Argentinta de Terapia Intensiva

Background: In previous experimental studies we have demonstrated that IMT504 is an immuno stimulating oligonucleotide that increases the cytokines response and the co-stimulatory molecules expression in vitro and in vivo.  We evaluate the effect of IMT504 in an experimental sepsis model. Methods: 28 Sprague Dawley rats were used. On the 0 day the animals were inoculated intraperitoneal with E. coli 045K1H10 or normal saline. On the first day, half of the animals that had been inoculated with bacteria, received IMT504 (Group 4) and the rest normal saline (Group 3). The animals that had been initially inoculated with normal saline (Group 1 and 2) received normal saline or IMT504. On day 4, the rats were killed. We carried out histologic studies on different organs specimens. The grade of histological injury was evaluated by a score. The serum levels of the cytokines IL-10, IL-6, TNF-a, GM-CSF and other common biochemical parameters were measured. Lymphocytes B (CD19+) CD40 expression was determine by flux citometry (Scalibur Scan, BD, USA). The results were compared by Student test or Mann-Whitney U test. Results: No significant differences of mortality, weight and serum levels of IL-6, GMC-SF, IL-10 and TNF-a were found between the two peritonitis groups on the fourth day. The IMT504 group had a higher number of lymphocytes and monocytes (p<0.01). Lymphocytes B CD40 expression was significant higher in the peritonitis IMT 504 rats (p = 0.006). The liver microscopic assessment showed lower necrosis, lower esteatosis and lower lobular inflammation (p = 0.01) in the IMT 504 group (Group 4). Conclusion: These results suggest an IMT504 tendency to regulate the cells that play a role in the sepsis inflammatory response and also a liver protection effect during the septic injury. Since our data are histological and biochemical we can only speculate on the functional significance of our findings.