Decreased production of neutrophil defensins and increased bacterial translocation in severely burned patients (89.33)

Abstract α-Defensins are antimicrobial peptides produced by human neutrophils (HNPs). Because severely burned patients are greatly susceptible to gut-associated infections, in this study, the role of HNPs on the resistance of burn patients to bacterial translocation was investigated. PMN were isolated from peripheral blood of severely burned patients, as previously described. These cells (2 x 106 cells/mouse) were inoculated to X-irradiated and decontaminated NOD-SCID IL-2rγ-/- mice (BP-chimeras) orally infected with 106 CFU/mouse of Enterococcus faecalis. The mortality rates of the chimeras were compared with those of chimeras created with healthy donor PMN (H-chimeras). Also, without any stimulation, PMN (1 x 106 cells/ml) were cultured for 18 hrs, and HNP 1-3 in their culture fluids were measured by ELISA. In the results, a 100% mortality rate was demonstrated in a group of BP-chimeras orally infected with 106 CFU/mouse of E. faecalis, while all of H-chimeras survived after the same infection. Healthy donor PMN produced 35.1 ng/ml of HNP 1-3. However, PMN from 5 out of 18 burned patients did not produce HNPs, and trace amounts of HNP 1-3 were produced by PMN from other 13 out of 18 burned patients. These results indicate that the abilities of PMN to produce HNPs are impaired in severely burned patients, and the susceptibility of thermally injured patients to enterococcal translocation may be influenced by the impaired HNP production.