Transplantation proceedings

The effect of immunosuppression on manifestations of sepsis in an animal model of cecal ligation and puncture.

PMID 23498819


The diagnosis of sepsis is difficult in immunocompromised patients owing to their modified response to infection. Our experiment in minipigs was designed to compare responses to sepsis between experimental groups of septic minipigs with and without immunosuppression. Minipigs with identical baseline parameters were randomized into 3 groups: Sepsis (n = 10); immunosuppression (n = 11), including cyclosporine, methylprednisolone, and mycophenolate mofetil treatment before surgery, and a sham group (n = 6). Sepsis was induced by cecal ligation and puncture (CLP). We recorded selected clinical and laboratory parameters up to 24 hours postoperatively. All CLP animals developed septic shock with a febrile response, tachycardia, and hypotension requiring noradrenaline administration. The hemodynamic responses to sepsis in septic groups with and without immunosuppression were similar. Noradrenaline infusion was started on average later in the immunosuppression than in the group without immunosuppression; however, the difference was not significant. The kinetics of the plasma levels of most selected cytokines and C-reactive protein were similar in both septic groups. At 10 hours after surgery, the immunosuppression group showed significantly lower interleukin (IL)-6 levels compared with the sepsis group. At 19, 22, and 25 hours after surgery immunosuppressed animals displayed significantly greater increases in IL-10 levels compared with the cohort without immunosuppression. CLP is a simple, reproducible model of sepsis in minipigs. All CLP animals developed sepsis within 24 hours on average. Significant differences in IL-6 and IL-10 plasma levels were recorded between septic animals with versus without immunosuppression.