Effect of Transforming Growth Factor-β Neutralization on Survival and Bacterial Clearance in a Murine Model of Pseudomonas aeruginosa Burn Wound Infection

Abstract

Transforming growth factor-β (TGF-β), a cytokine with anti-inflammatory properties, may contribute to postburn immunosuppression. This study was designed to determine whether neutralizing TGF-β in burned mice could improve resistance to infection. C57BL/6J mice received a 35% TBSA flame burn under isoflurane anesthesia. Four days after injury, mice were treated with TGF-β antibody or nonspecific IgG. On day 5 after burn injury, mice were inoculated with Pseudomonas aeruginosa at the burn wound site or received intraperitoneal injection with P. aeruginosa. Mice treated with anti-TGF-β exhibited significantly improved survival compared with mice treated with nonspecific IgG after challenge with P. aeruginosa at the burn wound site or after intraperitoneal injection of P. aeruginosa. In mice with burn wound infections, bacterial counts in burn wounds, blood, and lung were decreased in mice treated with anti-TGF-β compared with mice treated with control IgG. Bacterial counts in lung and blood after intraperitoneal challenge with P. aeruginosa also were significantly lower in burned mice treated with anti-TGF-β compared with those treated with nonspecific IgG. Our data suggest that neutralization of TGF-β at 4 days after burn injury in mice improves local and systemic clearance of P. aeruginosa and enhances survival after P. aeruginosa challenge.