title: Mechanical ventilation of healthy rats suppresses peripheral immune function.
abstract: This study was designed to investigate the possible effect of injurious mechanical ventilation on peripheral immune function of healthy rats. Three ventilation strategies were compared: 1) low peak inspiratory pressure (PIP)/positive end-expiratory pressure (PEEP); 2) high PIP/PEEP; and 3) high PIP/zero PEEP (ZEEP). As a reference group, healthy, nonventilated, sham-operated, anaesthetised rats were used. After 4 h, rats were sacrificed and macrophage inflammatory protein (MIP)-2 levels in lung and plasma were determined. Peripheral immune function was determined by measurement of splenic natural killer (NK) activity, mitogen-induced splenocyte proliferation and in vitro cytokine production. All immune measurements in the low PIP/PEEP group did not differ from the immune measurements in the reference group. High PIP strategies, irrespective of applied PEEP, enhanced MIP-2 levels in lung and plasma. NK cell activity, mitogen-induced splenocyte proliferation and MIP-2 and interleukin (IL)-10 production significantly decreased after high PIP/PEEP ventilation. In the high PIP/ZEEP-ventilated group, the decrease in splenocyte proliferation, MIP-2 and IL-10 production and NK cell activity was more pronounced and interferon-gamma production was also significantly lower than in the low PIP/PEEP group. These data show that high positive inspiratory pressure ventilation induces an inflammatory response in the lung, whereas at the same time the peripheral immune response is downregulated. Ventilator-induced peripheral immune suppression may contribute to poor outcome in acute respiratory distress syndrome patients.
authors.affiliation: Paediatric Intensive Care Unit, University Medical Centre, Utrecht, the Netherlands.
authors.forename: H A
authors.initials: HA
authors.lastname: Vreugdenhil
authors.forename: C J
authors.initials: CJ
authors.lastname: Heijnen
authors.forename: F B
authors.initials: FB
authors.lastname: Plötz
authors.forename: J
authors.initials: J
authors.lastname: Zijlstra
authors.forename: N J
authors.initials: NJ
authors.lastname: Jansen
authors.forename: J J
authors.initials: JJ
authors.lastname: Haitsma
authors.forename: B
authors.initials: B
authors.lastname: Lachmann
authors.forename: A J
authors.initials: AJ
authors.lastname: van Vught
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001794:Blood Pressure; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054426:Chemokine CXCL2; D016207:Cytokines / Q000096:biosynthesis; D007107:Immune System / Q000502:physiology*; D007249:Inflammation; D007694:Killer Cells, Natural / Q000502:physiology; D008934:Mitogens / Q000494:pharmacology; D015846:Monokines / Q000032:analysis; D010100:Oxygen / Q000097:blood; D010366:Peak Expiratory Flow Rate; D011175:Positive-Pressure Respiration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D015415:Biomarkers; D054426:Chemokine CXCL2; D016207:Cytokines; D008934:Mitogens; D015846:Monokines; D010100:Oxygen