CpG Oligonucleotides Activate the Immune Response in Burned Mice

Abstract

Immunosuppression after burn injury increases the risk of sepsis and multiple organ failure. We examined changes of immune function in mice after burn injury and investigated the immunostimulatory effect of oligodeoxynucleotides containing CpG motifs. Male BALB/c mice (8-10 wk old) received a full-thickness burn to 20% of their body surface area, after which the immunological parameters of splenic macrophages were evaluated. To assess the immunostimulatory effect of oligodeoxynucleotide treatment, splenic macrophages harvested from burned mice were incubated with oligodeoxynucleotides. Then cytokine production and major histocompatibility complex class II antigen expression were measured. To assess the in vivo effect of oligodeoxynucleotides, intraperitoneal administration was done on day 4 after burn injury, and class II antigen expression by splenic macrophages was measured 10 d later. Class II antigen expression and the synthesis of cytokines (interleukin-12, tumor necrosis factor-alpha, interleukin-6, and interleukin-1) by splenic macrophages were significantly reduced after burn injury, while incubation of splenic macrophages from burned mice with oligodeoxynucleotides partially enhanced the production of interleukin-12, tumor necrosis factor-alpha, interleukin-6, and interleukin-1. In addition, intraperitoneal administration of oligodeoxynucleotides enhanced class II antigen expression by splenic macrophages. The reduction of class II antigen expression and synthesis of cytokines (interleukin-12, tumor necrosis factor-alpha, interleukin-6, and interleukin-1) by splenic macrophages after burn injury was partially reversed by oligodeoxynucleotide treatment. Therefore, immunostimulatory oligodeoxynucleotides may be a potential treatment for post-burn immunosuppression.