title: Altered neutrophil functions in elderly patients during a 6-month follow-up period after a hip fracture.
abstract: BACKGROUND
  Fracture of the hip (HF) is a significant cause of morbidity and mortality in elderly individuals. HF is an acute stress that triggers a state of inflammation which may affect immune responses and physical recovery.
  
  
  METHODS
  Longitudinal study of the impact of HF on the functions of polymorphonuclear neutrophils (PMNs) in elderly subjects. Data were recorded prior to surgery, 6weeks and 6months later.
  
  
  RESULTS
  PMN functions were severely impaired shortly after HF (chemotaxis, phagocytosis, superoxide production) but there was a time-related recovery of some PMN functions (chemotaxis, phagocytosis) over time, except in the case of superoxide production. Whereas FcγRII (CD32) expression remained unchanged, FcγRIII (CD16) increased from low values before surgery to levels of controls 6months post-surgery. This was also the case for the C5a complement receptor and CD11b. TLR2 and TLR4 expressions were unchanged. Cytokine and chemokine secretions by stimulated PMN were altered. TNFα and IL-10 secretions were increased following HF but IL-8 secretion was decreased. Impaired PMN functions prior to surgery were related to alterations in PI3K and NF-κB signaling pathways. Recovery of these functions paralleled increased PI3K activity, although superoxide production remained low. Sustained activation of the NF-κB pathway by TNFα has been reported to involve upregulation of IKKβ kinase activity. Activated IKKβ kinase inhibits ERK1/2 and results in concomitant downstream inhibition of NADPH oxidase complex which can account for sustained impaired production of ROS in HF patients.
  
  
  CONCLUSIONS
  Our data showed that the stress caused by HF negatively affects initial PMN responses shortly after the event and that may negatively influence clinical outcomes such as resolving long-term inflammation and recovery, as well as explaining susceptibility to opportunistic infections.
authors: Division of Geriatrics and Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.
authors: Sarra
authors: S
authors: Baëhl
authors: Division of Geriatrics and Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.
authors: Hugo
authors: H
authors: Garneau
authors: Division of Geriatrics and Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.
authors: Aurélie
authors: A
authors: Le Page
authors: Division of Geriatrics and Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.
authors: Dominique
authors: D
authors: Lorrain
authors: Division of Geriatrics and Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.
authors: Isabelle
authors: I
authors: Viens
authors: Orthopedic Surgery Division, Centre Hospitalier Universitaire de l'Université de Sherbrooke, Sherbrooke (CHUS), Quebec J1H 5N4, Canada.
authors: Amy
authors: A
authors: Svotelis
authors: MRC-ARUK Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham, United Kingdom.
authors: Janet M
authors: JM
authors: Lord
authors: MRC-ARUK Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham, United Kingdom.
authors: Anna C
authors: AC
authors: Phillips
authors: Orthopedic Surgery Division, Centre Hospitalier Universitaire de l'Université de Sherbrooke, Sherbrooke (CHUS), Quebec J1H 5N4, Canada.
authors: François
authors: F
authors: Cabana
authors: Singapore Immunology Network (SIgN), Biopolis, Agency for Science Technology and Research (A*STAR), Singapore.
authors: Anis
authors: A
authors: Larbi
authors: Department of Biochemistry, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.
authors: Gilles
authors: G
authors: Dupuis
authors: Division of Geriatrics and Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada. Electronic address: Tamas.Fulop@Usherbrooke.ca.
authors: Tamàs
authors: T
authors: Fülöp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002170:Canada; D016022:Case-Control Studies; D002633:Chemotaxis / Q000276:immunology*; D005260:Female; D006620:Hip Fractures / Q000378:metabolism / Q000473:pathology / Q000534:rehabilitation / Q000601:surgery; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D019637:Orthopedic Procedures / Q000379:methods / Q000534:rehabilitation*; D059035:Perioperative Period; D010587:Phagocytosis / Q000276:immunology*; D011183:Postoperative Complications / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D017452:Receptors, IgG / Q000378:metabolism; D020127:Recovery of Function / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C496124:FCGR3A protein, human; D016209:Interleukin-8; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D016753:Interleukin-10
keywords: Aging; Chemotaxis; Hip fracture; Inflammation; Neutrophil functions; Phagocytosis