A model of polymicrobial peritonitis that induces the proinflammatory and immunosuppressive phases of sepsis

BARRERA G; LANDONI V.I; MARTIRE GRECO D; CHIARELLA P; REISS R; GOMEZ S.A; ALVES.ROSA MF; REARTE B; ISTURIZ M.A; PALERMO M.S; FERNANDEZ G.C

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Año: 2010 p. 1280 - 1288

0019-9567

Severe sepsis is associated with early release of inflammatory mediators that contribute to the  morbidity and mortality observed during the first stages of this syndrome. Although sepsis is  a deadly, acute disease, high mortality rates have been observed in survivors displaying evidence of sepsis-induced immune deactivation. Although the contribution of experimental  models to the knowledge of pathophysiological and therapeutic aspects of human sepsis is  undeniable, most of the current studies using animal models have focused on the acute, pro- inflammatory phase. We developed a murine model that reproduces early acute phases but 34 also long-term consequences of human sepsis. We induced a polymicrobial acute peritonitis  (AP) by establishing a surgical connection between the cecum and the peritoneum allowing  the exit of intestinal bacteria. Using this model we observed an acute phase with high  mortality, leucopenia, increased IL-6, bacteremia, and neutrophil activation. A peak of leukocytosis at day 9-10 revealed the persistence of the infection within the lung and liver, with clear signs of inflammatory hepatic damage as shown by histological examination. Long-term (20 days) derangements in both innate and adaptive immune responses were  found, as demonstrated by impaired systemic TNF-a production in response to an  inflammatory stimulus, decreased primary humoral immune response and T cell proliferation,  associated with an increased number of myeloid suppressor cells (Gr-1+ CD11b+) in the  spleen, and low clearance capacity. This model provides a good approach to attempt novel  therapeutic interventions directed to augment host immunity during late sepsis.