Intubation/mechanical ventilation after burn contributes to pneumonia-related infection. While postburn presence/absence of endotoxin has been described, inactivation of TLR4 signaling has been shown to improve postburn organ function, suggesting that LPS participates in burn-related susceptibility to infection. We hypothesized that bactericidal/permeability-increasing protein (rBPI) given postburn would attenuate myocardial inflammation/dysfunction associated with postburn septic challenge given 7 days postburn. Rats were given burn over 40% TBSA, lactated Ringer's 4ml/kg/% burn; burns received either vehicle or rBPI, 1mg/kg/hr for 48 hrs postburn. Postburn day 7, subgroups of burns and shams were given intratracheal Klebsiella pneumoniae, 4x10⁶ CFU to produce burn complicated by sepsis; additional sham and burn subgroups received intratracheal vehicle to produce sham sepsis. Vehicle-treated groups: 1) sham burn + sham sepsis; 2) sham burn + sepsis; 3) burn + sham sepsis; 4) burn + sepsis. rBPI treated groups; 5) sham burn + sham sepsis; 6) sham burn + sepsis; 7) burn + sham sepsis; 8) burn + sepsis. Cardiomyocyte cytokine secretion and myocardial function were studied 24 hrs after septic challenge, postburn day 8. Pneumonia-related infection 8 days after vehicle-treated burn produced myocytel cytokine secretion (pg/ml), indicated by increased myocyte TNF-, 549±46; IL-1, 50±8; IL-6, 286±3 levels compared to levels in sham myocytes (TNF-, 88±11; IL-1, 7±1; IL-6, 74±10; p<0.05). Contractile dysfunction was evident from lower LVP/±dP/dt values in this group compared to sham. rBPI attenuated myocyte cytokine responses to septic challenge and improved contractile function, suggesting that burn-related mobilization of microbial-like products contribute to postburn susceptibility to infection.