title: A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged.
abstract: The elderly are particularly susceptible to trauma, and their outcomes are frequently dismal. Such patients often have complicated clinical courses and ultimately die of infection and sepsis. Recent research has revealed that although elderly subjects have increased baseline inflammation as compared with their younger counterparts, the elderly do not respond to severe infection or injury with an exaggerated inflammatory response. Initial retrospective analysis of clinical data from the Glue Grant trauma database demonstrated that despite a similar frequency, elderly trauma patients have worse outcomes to pneumonia than younger subjects do. Subsequent analysis with a murine trauma model also demonstrated that elderly mice had increased mortality after posttrauma Pseudomonas pneumonia. Blood, bone marrow, and bronchoalveolar lavage sample analyses from juvenile and 20-24-mo-old mice showed that increased mortality to trauma combined with secondary infection in the aged are not due to an exaggerated inflammatory response. Rather, they are due to a failure of bone marrow progenitors, blood neutrophils, and bronchoalveolar lavage cells to initiate and complete an emergency myelopoietic response, engendering myeloid cells that fail to clear secondary infection. In addition, elderly people appeared unable to resolve their inflammatory response to severe injury effectively.
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Dina C
authors.initials: DC
authors.lastname: Nacionales
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Benjamin
authors.initials: B
authors.lastname: Szpila
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ungaro
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Lopez
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Lori F
authors.initials: LF
authors.lastname: Gentile
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Angela L
authors.initials: AL
authors.lastname: Cuenca
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Erin
authors.initials: E
authors.lastname: Vanzant
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Brittany
authors.initials: B
authors.lastname: Mathias
authors.affiliation: Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Jeevan
authors.initials: J
authors.lastname: Jyot
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Donevan
authors.initials: D
authors.lastname: Westerveld
authors.affiliation: Department of Anesthesia, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Azra
authors.initials: A
authors.lastname: Bihorac
authors.affiliation: Institute on Aging, University of Florida College of Medicine, Gainesville, FL 32610; and.
authors.forename: Anna
authors.initials: A
authors.lastname: Joseph
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Alicia
authors.initials: A
authors.lastname: Mohr
authors.affiliation: Department of Pathology, University of Florida College of Medicine, Gainesville, FL 32610.
authors.forename: Lizette V
authors.initials: LV
authors.lastname: Duckworth
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Moore
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Henry V
authors.initials: HV
authors.lastname: Baker
authors.affiliation: Institute on Aging, University of Florida College of Medicine, Gainesville, FL 32610; and.
authors.forename: Christiaan
authors.initials: C
authors.lastname: Leeuwenburgh
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610; moldawer@surgery.ufl.edu.
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Scott
authors.initials: S
authors.lastname: Brakenridge
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610;
authors.forename: Philip A
authors.initials: PA
authors.lastname: Efron
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007109:Immunity / Q000235:genetics / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D038042:Myelopoiesis / Q000235:genetics / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D053717:Pneumonia, Ventilator-Associated / Q000209:etiology / Q000276:immunology; D011552:Pseudomonas Infections / Q000235:genetics / Q000276:immunology / Q000401:mortality; D012771:Shock, Hemorrhagic / Q000150:complications / Q000276:immunology*; D015996:Survival Rate; D059467:Transcriptome / Q000235:genetics / Q000276:immunology; D014947:Wounds and Injuries / Q000150:complications / Q000276:immunology*