Anti-interleukin-6 antibody treatment improves survival during gut-derived sepsis in a time-dependent manner by enhancing host defense

Abstract

To determine the in vivo neutralizing activities of anti-interleukin-6 (IL-6) antibody on survival rate and host defense in a clinically relevant model of infection. Prospective, randomized, experimental animal study. University and Shriners Burns Institute research laboratories. Two hundred seventy-six adult, female Balb/c mice. Balb/c mice were treated with 10 micrograms of antimurine IL-6 antibody, nonspecific murine immunoglobulin G (IgG), or placebo at 2, 4, or 8 hrs after they underwent bacterial challenge by gavage of 10(10) Escherichia coli and thermal injury. The survival rate was determined. The number of viable translocated bacteria, the total amount of translocation, and the percentage of bacteria that survived were also studied in different tissues. Survival rate after burn and gavage was significantly improved in animals treated with antimurine IL-6 antibody at 2 and 4 hrs but not at 8 hrs after injury compared with control animals treated with nonspecific IgG or saline. The IL-6 serum concentration was significantly lower after burn and gavage in the animals treated 2 and 4 hrs after injury compared with nontreated animals. Better killing of translocated bacteria was observed in the tissues of animals treated with antimurine IL-6 antibody 2 hrs after injury. Treatment with antimurine IL-6 antibody at 2 and 4 hrs after injury, but not at 8 hrs after injury, positively affects outcome during gut-derived sepsis. Moreover, the beneficial effect of treatment after 2 hrs was related to an enhanced clearance of translocated bacteria.