title: Mechanical ventilation with high tidal volume or frequency is associated with increased expression of nerve growth factor and its receptor in rabbit lungs.
abstract: OBJECTIVE
  Nerve growth factor (NGF), a neurotrophin, is induced in lung cells by proinflammatory cytokines, and has a role in bronchial hyperreactivity and lung tissue repair. Ventilation induced lung injury, on the other hand, is known to increase the levels of proinflammatory cytokines in the lungs. We investigated whether, and to what extent, various degrees of lung injury induced by short-term ventilation affect NGF levels in the lung tissue of adolescent rabbits.
  
  
  METHODS
  The rabbits were randomized to different modes of ventilation: (1) CON: normal ventilation for 30 min; (2) NVT: normal ventilation for 6 hr; (3) HFQ: ventilation for 6 hr at double frequency, but normal tidal volume (VT); and (4) HVT: 6 hr ventilation at double VT but normal frequency.
  
  
  RESULTS
  NGF protein was detected in bronchoalveolar lavage fluid (BALF) and lung tissue in all animals. Ventilation for 6 hr significantly increased NGF levels, in both BALF and lung tissue, in the HFQ and HVT groups as compared to control (P < 0.05). The maximum increase in BALF NGF was seen in the HVT group (P = 0.02 vs. CON and NVT groups, and P = 0.05 vs. HFQ). A parallel increase in interleukin 1-beta (IL1-beta) was observed. Expression of the high-affinity NGF-receptor, tropomyosin-related kinase A (TrkA), was also upregulated in these two groups.
  
  
  CONCLUSIONS
  Injurious modes of mechanical ventilation upregulate NGF and its receptor TrkA in rabbit lungs, and IL1-beta may be a mediator for this response. We speculate that this increase in NGF level may translate into the development of bronchial hyperreactivity.
authors.affiliation: Department of Neonatology, Dr. von Hauner's Children's Hospital, Ludwig-Maximilians University, Munich D-80337, Germany.
authors.forename: Rashmi A
authors.initials: RA
authors.lastname: Mittal
authors.forename: George
authors.initials: G
authors.lastname: Simbruner
authors.forename: Johan
authors.initials: J
authors.lastname: Smith
authors.forename: Bernadette
authors.initials: B
authors.lastname: Simbruner
authors.forename: Andreas
authors.initials: A
authors.lastname: Holzinger
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D053583:Interleukin-1beta / Q000378:metabolism; D055370:Lung Injury / Q000209:etiology* / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D012121:Respiration, Artificial / Q000009:adverse effects*; D013990:Tidal Volume; D015854:Up-Regulation
chemical_list: D053583:Interleukin-1beta; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D020917:Receptor, trkA